#METABOLOMICS WORKBENCH tverkerke_20240429_123306 DATATRACK_ID:4799 STUDY_ID:ST003264 ANALYSIS_ID:AN005348 PROJECT_ID:PR002026 VERSION 1 CREATED_ON June 17, 2024, 5:26 pm #PROJECT PR:PROJECT_TITLE SLC25A48 controls mitochondrial choline import and metabolism PR:PROJECT_SUMMARY Choline is an essential nutrient for cellular metabolism, including the PR:PROJECT_SUMMARY biosynthesis of phospholipids, neurotransmitters, and one-carbon metabolism. A PR:PROJECT_SUMMARY critical step in choline catabolism is the mitochondrial import and synthesis of PR:PROJECT_SUMMARY choline-derived methyl donors, such as betaine. However, the underlying PR:PROJECT_SUMMARY mechanisms and the biological significance of mitochondrial choline metabolism PR:PROJECT_SUMMARY remain poorly understood. Here, we report that a previously uncharacterized PR:PROJECT_SUMMARY mitochondrial inner-membrane protein, SLC25A48, controls mitochondrial choline PR:PROJECT_SUMMARY transport and catabolism in vivo. We show that SLC25A48 is highly expressed in PR:PROJECT_SUMMARY brown adipose tissue and is required for whole-body cold tolerance, PR:PROJECT_SUMMARY thermogenesis, mitochondrial respiration, and mitochondrial membrane integrity. PR:PROJECT_SUMMARY Choline uptake into the mitochondria via SLC25A48 facilitates the synthesis of PR:PROJECT_SUMMARY betaine and purine nucleotides, whereas loss of SLC25A48 resulted in increased PR:PROJECT_SUMMARY production of reactive oxygen species and imbalanced mitochondrial lipids. PR:PROJECT_SUMMARY Notably, human cells carrying a single nucleotide polymorphism on the SLC25A48 PR:PROJECT_SUMMARY gene and cancer cells lacking SLC25A48 exhibited elevated oxidative stress and PR:PROJECT_SUMMARY impaired cell proliferation. Together, the present study identified SLC25A48 as PR:PROJECT_SUMMARY a mitochondrial carrier that mediates choline catabolism and plays a critical PR:PROJECT_SUMMARY role in mitochondrial function and cell survival. PR:INSTITUTE Beth Israel Deaconess Medical Center PR:LAST_NAME Verkerke PR:FIRST_NAME Anthony PR:ADDRESS 330 Brookline Avenue, Boston, Massachusetts, 02215, USA PR:EMAIL averkerk@bidmc.harvard.edu PR:PHONE 7159231910 #STUDY ST:STUDY_TITLE SLC25A48 controls mitochondrial choline import and metabolism ST:STUDY_SUMMARY Choline is an essential nutrient for cellular metabolism, including the ST:STUDY_SUMMARY biosynthesis of phospholipids, neurotransmitters, and one-carbon metabolism. A ST:STUDY_SUMMARY critical step in choline catabolism is the mitochondrial import and synthesis of ST:STUDY_SUMMARY choline-derived methyl donors, such as betaine. However, the underlying ST:STUDY_SUMMARY mechanisms and the biological significance of mitochondrial choline metabolism ST:STUDY_SUMMARY remain poorly understood. Here, we report that a previously uncharacterized ST:STUDY_SUMMARY mitochondrial inner-membrane protein, SLC25A48, controls mitochondrial choline ST:STUDY_SUMMARY transport and catabolism in vivo. We show that SLC25A48 is highly expressed in ST:STUDY_SUMMARY brown adipose tissue and is required for whole-body cold tolerance, ST:STUDY_SUMMARY thermogenesis, mitochondrial respiration, and mitochondrial membrane integrity. ST:STUDY_SUMMARY Choline uptake into the mitochondria via SLC25A48 facilitates the synthesis of ST:STUDY_SUMMARY betaine and purine nucleotides, whereas loss of SLC25A48 resulted in increased ST:STUDY_SUMMARY production of reactive oxygen species and imbalanced mitochondrial lipids. ST:STUDY_SUMMARY Notably, human cells carrying a single nucleotide polymorphism on the SLC25A48 ST:STUDY_SUMMARY gene and cancer cells lacking SLC25A48 exhibited elevated oxidative stress and ST:STUDY_SUMMARY impaired cell proliferation. Together, the present study identified SLC25A48 as ST:STUDY_SUMMARY a mitochondrial carrier that mediates choline catabolism and plays a critical ST:STUDY_SUMMARY role in mitochondrial function and cell survival. ST:INSTITUTE Harvard Medical School ST:LAST_NAME Verkerke ST:FIRST_NAME Anthony ST:ADDRESS 330 Brookline Avenue, CLS 730 ST:EMAIL averkerk@bidmc.harvard.edu ST:PHONE 7159231910 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 SU:GENDER Male #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 - Serum_1 Genoptye:Control | Sample source:Serum RAW_FILE_NAME=Serum_1.RAW SUBJECT_SAMPLE_FACTORS - Serum_2 Genoptye:Control | Sample source:Serum RAW_FILE_NAME=Serum_2.RAW SUBJECT_SAMPLE_FACTORS - Serum_3 Genoptye:Control | Sample source:Serum RAW_FILE_NAME=Serum_3.RAW SUBJECT_SAMPLE_FACTORS - Serum_4 Genoptye:Control | Sample source:Serum RAW_FILE_NAME=Serum_4.RAW SUBJECT_SAMPLE_FACTORS - Serum_5 Genoptye:Control | Sample source:Serum RAW_FILE_NAME=Serum_5.RAW SUBJECT_SAMPLE_FACTORS - Serum_6 Genoptye:Control | Sample source:Serum RAW_FILE_NAME=Serum_6.RAW SUBJECT_SAMPLE_FACTORS - Serum_7 Genoptye:Control | Sample source:Serum RAW_FILE_NAME=Serum_7.RAW SUBJECT_SAMPLE_FACTORS - Serum_8 Genoptye:Control | Sample source:Serum RAW_FILE_NAME=Serum_8.RAW SUBJECT_SAMPLE_FACTORS - Serum_9 Genoptye:SLC25A48-KO | Sample source:Serum RAW_FILE_NAME=Serum_9.RAW SUBJECT_SAMPLE_FACTORS - Serum_10 Genoptye:SLC25A48-KO | Sample source:Serum RAW_FILE_NAME=Serum_10.RAW SUBJECT_SAMPLE_FACTORS - Serum_11 Genoptye:SLC25A48-KO | Sample source:Serum RAW_FILE_NAME=Serum_11.RAW SUBJECT_SAMPLE_FACTORS - Serum_12 Genoptye:SLC25A48-KO | Sample source:Serum RAW_FILE_NAME=Serum_12.RAW SUBJECT_SAMPLE_FACTORS - Serum_13 Genoptye:SLC25A48-KO | Sample source:Serum RAW_FILE_NAME=Serum_13.RAW SUBJECT_SAMPLE_FACTORS - Serum_14 Genoptye:SLC25A48-KO | Sample source:Serum RAW_FILE_NAME=Serum_14.RAW SUBJECT_SAMPLE_FACTORS - Serum_15 Genoptye:SLC25A48-KO | Sample source:Serum RAW_FILE_NAME=Serum_15.RAW SUBJECT_SAMPLE_FACTORS - Serum_16 Genoptye:SLC25A48-KO | Sample source:Serum RAW_FILE_NAME=Serum_16.RAW #COLLECTION CO:COLLECTION_SUMMARY Standard chow fed mice were fasted for four hours prior to serum or tissue CO:COLLECTION_SUMMARY collection. CO:SAMPLE_TYPE Serum #TREATMENT TR:TREATMENT_SUMMARY Samples are from wild-type or SLC25A48-KO male mice fed a standard chow diet. TR:TREATMENT_SUMMARY Mice were fasted for four hours prior to sample collection. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY 10 µL serum was mixed with 90 µL extraction solvent of methanol: acetonitrile: SP:SAMPLEPREP_SUMMARY water 40: 40: 20 at -20 ˚C, and then vigorously vortexed. All samples were then SP:SAMPLEPREP_SUMMARY conditioned to -4 ˚C, and centrifuged at 16,000 rpm/min. The supernatant was SP:SAMPLEPREP_SUMMARY transferred to LC-MS tubes for analysis. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY Waters XBridge BEH Amide XP Column (150 x 2.1mm, 2.5um) with guard column (5mm x CH:CHROMATOGRAPHY_SUMMARY 2.1mm, 2.5 µm) CH:CHROMATOGRAPHY_TYPE HILIC CH:INSTRUMENT_NAME Thermo Vanquish CH:COLUMN_NAME Waters XBridge BEH Amide XP (150 x 2.1mm, 2.5um) CH:SOLVENT_A 95% Water, 5% Acetonitrile; 10 mM ammonium acetate and 10 mM ammonium hydroxide CH:SOLVENT_B 20% Water, 80% Acetonitrile; 10 mM ammonium acetate and 10 mM ammonium hydroxide CH:FLOW_GRADIENT 0 - 3 min, 100% B; 3.2 - 6.2 min, 90% B; 6.5 - 10.5 min, 80% B; 10.7 - 13.5 min, CH:FLOW_GRADIENT 70% B; 13.7 - 16 min, 45% B; and 16.5 - 22 min, 100% B CH:FLOW_RATE 0.3 mL/ min CH:COLUMN_TEMPERATURE 4˚C #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive HF MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE UNSPECIFIED MS:MS_COMMENTS The mass spectrometry used was Q Exactive HF (Thermo Fisher Scientific, San MS:MS_COMMENTS Jose, CA), and scanned from 70 to 1000 m/z with switching polarity. The MS:MS_COMMENTS resolution was 120,000. Metabolites were identified based on accurate mass and MS:MS_COMMENTS retention time using an in-house library, and the software used was EI-Maven MS:MS_COMMENTS (Elucidata, Cambridge, MA). #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS Peak area MS_METABOLITE_DATA_START Samples Serum_1 Serum_2 Serum_3 Serum_4 Serum_5 Serum_6 Serum_7 Serum_8 Serum_9 Serum_10 Serum_11 Serum_12 Serum_13 Serum_14 Serum_15 Serum_16 Factors Genoptye:Control | Sample source:Serum Genoptye:Control | Sample source:Serum Genoptye:Control | Sample source:Serum Genoptye:Control | Sample source:Serum Genoptye:Control | Sample source:Serum Genoptye:Control | Sample source:Serum Genoptye:Control | Sample source:Serum Genoptye:Control | Sample source:Serum Genoptye:SLC25A48-KO | Sample source:Serum Genoptye:SLC25A48-KO | Sample source:Serum Genoptye:SLC25A48-KO | Sample source:Serum Genoptye:SLC25A48-KO | Sample source:Serum Genoptye:SLC25A48-KO | Sample source:Serum Genoptye:SLC25A48-KO | Sample source:Serum Genoptye:SLC25A48-KO | Sample source:Serum Genoptye:SLC25A48-KO | Sample source:Serum Glycine 1225430 2320490.75 1779886.62 2194564.25 2097928.5 1515518 1748514.12 985511.19 1433609.62 1154625 2000670.88 1662599.5 3147505 1508015.38 1857567.12 1341462.5 Pyruvate 23924456 32530288 27897256 28749728 23914318 33709308 45257248 16863430 20940762 30035338 37011460 30044382 28872898 28634270 23025056 33156634 Alanine 6153598.5 12505721 5792692 6671501.5 7369422.5 6649625.5 6900876 4180097.75 6809190 6305382.5 6944698.5 7618906.5 10712536 5455919.5 6637168 4714727.5 Lactate 897720512 1421378560 740421120 1074212992 942787392 986395456 944792768 494441504 917643456 907844096 776189376 1173278336 1133771904 529590912 641828544 932300224 Acetoacetate 2522249.75 1199765.38 3614415 2821719.75 1881129.62 1303955 1545122 3027213 1248155.5 1598518.12 4179529.25 2082808.38 1644289.62 3434839.75 2751486.75 1855312.38 N-Formylglycine 48213.83 194062.7 40914.44 39255.39 60000.55 53730.72 87635.46 44512.47 47868.86 67911.65 80048.59 45528.39 40386.44 38875.89 54144.69 42294.77 3-Hydroxybutyric acid 36672364 17791076 23687864 38528308 20304638 15974096 12474229 27003798 15072616 13457024 33158678 24499342 21835544 25903686 29239418 27354544 3-hydroxyisobutyric acid 7627331.5 7363322.5 6746913.5 12512789 9473919 12315915 11506080 6742092 3978191 6218531.5 10984764 8416761 9533439 8506153 11908183 7660634.5 Serine 5331298.5 8674439 5543226 5900095.5 5856850.5 4595102 4689342.5 4012436.25 5545843 4290497.5 7951633.5 5727254.5 8747435 3444635.75 5220254.5 3510365.75 Glycerate 360339.25 557153.06 499962 520945.5 510668.09 609595.06 804318.06 435740.59 412617.5 556681.31 495700.12 521573.91 500766.38 531999.12 584590.69 653914.44 Fumarate 902034.31 3514500.75 1428043.5 1571090.38 1614615.5 2330940.75 2119228 1109031.38 1925452 1407355 1077858 1222593.12 2365343 1292742.62 1533362.38 1769987.38 3-methyl-2-oxobutyrate 9568652 8155066.5 8929957 10307959 9992607 9297685 9828153 7790877.5 8306737.5 12021008 9666099 8345210.5 9098435 7309150 7939652 8579067 N-Acetylglycine 9592261 7316222 6987802.5 11737080 9162757 8158904 5969186 4704361.5 8459385 6559688 9402489 8637463 7870204 6130729.5 6163034.5 6921804.5 Guanidineacetic Acid 20098.93 34530.57 13606.94 13946.6 22800.01 25237.63 29815.38 17543.12 19925.82 22186.01 36279.94 27979.98 42039.3 41619.27 43552.34 26750.56 Valine 5599345.5 9047671 9656912 8440485 9836693 8965237 8987136 5674174.5 6655985.5 7795145.5 8341627.5 8559016 7982160 4592457.5 8133518.5 5890592 Succinic acid 14138803 48744908 12442873 27875234 30114214 24029672 22363118 10312740 26148592 22740890 11975687 37296000 37731612 8881404 16863382 24239962 Taurine 26588304 34249612 22826010 26014742 29387550 24163808 21871486 15066304 29291728 29675080 24251014 29779742 26878992 17514542 24573850 19289930 Thymine 83460.62 225422.38 102881.38 105111.52 69282.7 167029.78 162292.61 169424.97 82425.02 40182.16 161259.8 67932.91 152718.86 117783.07 232642.58 76180.2 Pyroglutamate 9123253 7776074 7554787.5 7156044 8293232 5751000 4901640 4417456.5 9339349 7099004.5 6469894 7471710.5 6775626.5 4530446.5 6595135.5 3629247.25 N-Acetyl-L-alanine 337069.12 385219.34 202437.92 257536.48 227577.12 290032.59 348687.22 161349.89 241962.61 235993.3 378783.5 469202.62 380565.75 231084.2 388221.12 163993.31 trans-4-Hydroxy-L-proline 445262 576729.81 309581.59 476889.41 436664.72 410271.25 480387.22 175246.92 449541.12 257288.7 380943.25 589785.12 501984.25 167291.72 233364.55 216247.39 Isoleucine 4214249 7737926.5 7358188.5 6041828.5 7193002.5 6932341.5 5965669.5 4644330.5 5509638.5 5511961.5 6026534 6737512 6517610 3570500 5670576 5095492.5 Leucine 8779802 13656835 12559192 11101337 13431016 12752152 11121448 8564304 10370985 10059828 10520279 13000497 11250073 6355056 10989605 8896201 Oxaloacetate 14577.54 23849.82 21438.47 18848.35 22459.9 37052.34 45562.31 18445.49 23555.29 25985.62 23666.31 14360.56 25823.92 25664.81 34176.66 20392.23 Ethylmalonic acid 2293255.5 2432652.75 2538425.25 2409474.75 2752226.25 3473949 3555864.75 2589632.5 2168420.25 2386665.75 1946281.38 2351958.75 2119108.25 2157073.75 1913601.38 2676817 3-Ureidopropionic acid 81978.09 118152.93 74913.9 77788.84 45314.65 86564.9 136633.09 32537.33 47019.14 53353.43 117470.63 200502.55 86961.38 69961.62 254413.75 75857.89 Asparagine 871579 2918424.75 1272046.5 1174382.62 1080888.38 1119312.88 1094632.62 979728 1016456.31 867116.5 2998925.75 1258366.62 3642845.25 1655290.88 2346534 872012.44 Aspartate 217564.08 227596.7 154832.52 206276.67 226384 208637.83 173988.7 102150.34 206285.69 194993.83 238941.89 284982.53 319341.53 125656.98 245013.45 109104.31 Malate 9701411 52811028 14138669 15596697 16376605 27173358 27055382 9535983 20698376 14931508 9744967 13066393 29543450 12080947 16399649 18837066 Urocanate 1531747.62 939215.31 900431 962132.69 811830.81 802237.19 615655.19 351802.41 1299889.38 789706.31 1020012 1075989.25 1051626.38 250567.14 610830.19 220915.83 O-Phosphoryethanolamine 302262.72 528164.25 176309 248628.48 257751.39 212770.06 162610.2 77703.6 312803.66 212841.23 302682.28 343235.94 303688.47 98512.26 107525.59 83607.98 3-Methylglutaconate 5276640 5789570 5847673.5 5385602 6439102 7938338 8724076 6165042 4921175 5533553.5 4290568 5392402.5 4890424.5 4898126.5 4232348.5 6423336 Alpha-Ketoglutarate 6251647.5 18255466 13521188 14132912 11104916 23177312 26409976 12729987 11365225 13553792 13728721 6021470.5 19614054 18235354 18876146 15825816 Glutamate 2680079 4912268.5 2018647.62 3146857 2968554.25 2506899 2055930.12 1341440.88 3009893.25 2607410.75 2967084 3708976.25 4907071.5 1666096.12 3167050.25 2084849.12 N-Acetyl-serine 1165878.5 1204946.12 1062298.75 1430260.88 1650429.12 1174123.38 1183712.5 577451.81 1058014.12 1032934.19 859041.81 1200385.38 849126.69 727103.25 976940.06 743006.31 Citramalate 1104728.38 2478533.75 1562377.38 1644900 1315329 2284506.75 3142481.75 1393061.38 1413970.62 1606573.5 1413222.12 1228067.5 1574182.62 1654811 1876571.62 1843224 Orotate 654942.69 811377.94 763567.81 610592.94 834607.56 1089270.38 1032941.44 489485.25 648208.06 992451.75 617046.25 576840.69 542793.69 728707.19 1000840 563333 Dihydroorotic acid 14745.04 25319.97 29689.14 19703.33 32490.88 45448.31 31041.97 25541.58 29339.17 24229.37 25659.69 20282.52 15174.39 23807.57 38434.71 21477.66 Allantoin 5925817.5 7731043.5 7679949.5 5470880.5 5706972 9248894 10473631 6033150 6010923.5 6743111.5 6018844 7373140.5 5046896 8069209.5 8892280 6967304 N-Methyl-L-glutamate 349664.53 328146.25 209298.58 516453.59 339914.66 476935.09 437761.75 297902.22 183058.83 190942.56 198281.12 201139.25 162587.86 124443.31 132597.38 267322.97 3-Hydroxy-3-methylglutarate 1402678.38 1852723.62 1242059.12 1841912 1345992.12 2211973 2536256.75 1389408.38 1089059.88 1329091.62 1548178.62 1782844.12 1338009.25 1114226.75 1338479.12 1398627.12 Fucose 1121395.75 524810.31 1452206.12 1220336.38 1685060.62 1307600.88 1639748.62 2077502.5 1113104.75 1428574 609797.38 1136895.38 715942 1101402.88 1401391.12 1615546.38 Phenylalanine 2507672.25 3729840.25 3185434 2821987.25 3446971.75 3332661.25 3258231.25 2584729.25 2717704 3063360 4195388 3206138 4279715.5 3342051 4798357.5 1951212.5 Uric acid 4451808.5 5107571.5 499535.41 1271242.38 2224630.25 829647.69 1619543 219580.17 1112799 2280300 1018536.31 3664274 3079926 684118 1950898.62 907921 Dihydroxyacetone phosphate 88592.65 91344.43 22648.88 44025.89 84176.47 20092.75 17403.6 7603.6 94895.56 51146.78 27323.55 67395.88 42831.11 12813.98 14308.85 2006.27 Glycerol 3-phosphate 467948.91 807194 277176.66 376559.91 480270.91 321390.78 309837.44 171527.17 428914.28 376448.03 311903.16 471544.97 366503.75 182570.17 230927 210634.94 N-Acetyl-Leucine 2714885.25 4113435 2514189.75 4458561.5 3990105.25 4457171.5 3594926.75 1701971 1976151.5 2287499.25 4142412.25 2850412.25 3806259 2312465 2242724.25 2229862 cis-aconitic acid 3517562.25 5087760.5 4619357.5 4163077.75 4162052.25 7185108 9226373 5376533.5 3617632 4686885.5 4464114.5 3282885.75 4762702.5 7677123.5 6421600 7468588.5 N-Acetyl-aspartate 533338.31 976078.31 413635.47 461905.91 472211.03 666747.25 756926 327612.06 575735.75 448517.28 417028.16 543839.19 503195.72 274254.22 274005.81 384883.34 Citrulline 1242398.5 1893332.5 2720482.75 1580101.12 1811602.62 2870878.75 3090268.75 1623647.88 1846932.62 1865087 2288515.75 1718975.62 2211793 2755493.5 2800108 1890104.12 Hippuric acid 612574 652641.94 478462.97 318240.66 666510.19 98583.51 122948.71 573175.19 1618303.62 1026492.19 199356.11 798381.5 166398.06 880649 495094.59 638959.56 Glucose 98359744 107298728 108691840 101887104 121513160 154507184 165149392 115910848 90478568 102045800 78880976 98476648 88432344 90895616 78457672 120454728 Tyrosine 2301219.25 5265264.5 2624278 2652532 3158636.75 2715542 2476331.75 2137834.25 3285070.75 2357479.5 3921933 3287822 4599758 2710961 3251220.75 2010534.12 Homovanillic acid 170010.55 500837.03 158331 185026.02 225734.8 336230.72 438736.03 124381.46 212647.33 236205.92 281226.72 184795.33 302965.91 261720.75 285726.84 144325.05 Galactitol 400126.03 636148.31 435269.91 414641.62 494715.09 488169.97 522279 429685.78 447525.62 425463.59 360434.5 363146.16 334037.66 468102.66 431392.5 427845.09 Acetylglutamine 550170.56 376259.66 516090.12 722996 684678.69 533066.25 560120.94 300876.03 674198.06 556116.19 335291.53 534032.62 326926.41 306056.09 487429.84 493343.5 N-Acetyl-glutamate 100903.24 193918.58 179150.83 220501.69 272887.88 340172.22 331409.88 180080.23 138573.98 219881.83 115307.04 127476.88 172484.27 129828.26 136901.42 166013.67 Acetylmethionine 78392.34 262462.12 58968.48 100081.96 103457.91 160847.45 138754.09 56145.41 89899.78 76554.69 104687.76 95068.26 168913.44 82884.74 92618.34 71000.46 Citrate 4620551.5 11191652 6900024 6705881.5 7464897.5 18138490 18594520 6135952.5 5706087.5 6878994.5 5321565.5 4416152.5 8351912 13832748 12706925 6529628 Glucuronic acid 1325324.38 1408714.62 1267122.88 1285396.12 1209967.12 1460412 1488992.5 737349.25 1544210 1164259.62 1216232.12 1214720.38 1014119.31 1120197 1014379.75 1131646.88 methyl beta-D-galactopyranoside 1167542.5 593331.56 831213.81 1088106.38 546125.19 506856.75 388783.91 815208.69 499956 382458 1068143 834470.44 687408.31 832814.94 913430.06 780667.5 Gluconate 2515087.75 2713027.75 1966528 4018402 3364880.75 1993261.62 2102066.75 1060445.38 2481401.75 1399160.38 2261128.25 2666093 2883080 1471063.12 4325328.5 1876996.62 Sebacic acid 203929.38 162822 68638.34 136882.31 58723.98 67136.51 54711.86 46612.44 54857.7 31189.93 83630.66 83254.37 73078.95 70343.97 37530.71 109734.87 Tryptophan 3733069.25 4411570.5 4727177.5 5203845.5 5819418 6400438 6967060 5841224 3152774 5975403.5 4548122.5 4166344.75 5797118.5 5268210 5636036.5 5350958 Indolelactate 312469.25 603230.12 249762.98 274682.66 382276.66 255861.05 279295.38 167482.62 536257.56 378880.72 358558.28 304867.62 303441.09 537652.25 436227.34 197873.3 N-Acetyl-L-phenylalanine 307831.38 2095307.38 454455.78 310185.88 473452.47 554976.56 603703.19 231347.3 458314.12 472084.09 985832.5 392099.09 1008785.19 349529.72 729680.69 316773 O-Succinyl-L-Homoserine 51160.7 73517.99 44165.34 90115.98 59867.32 94273.3 51500.14 27744.17 60668.28 49878.52 71282.17 32923.75 64445.75 44757.45 28250.22 71649.15 Pantothenate 367060.41 931434 565300.12 546927.94 560214.56 713700.69 802645.19 416651.22 423902.5 471033.75 561391.31 732594.81 793754.19 375265.38 854803 404910.62 Ribose 5-phosphate 493323.53 429084.03 62733.55 182329.67 594211.69 289693.22 264264.03 75188.3 583536.19 310266.78 125491.62 444714.22 321156.78 254640.8 445943 40013.61 Thymidine 192950.88 420500.41 253233.55 170481.12 153422.58 391218 332519.38 388851.62 163361.34 84503.68 285257.72 160751.77 272531.53 245595.69 471564 187171.55 Uridine 29531 43132.05 16693.51 18255.05 42266.29 112084.94 69197.74 66669.1 29546.74 34403.98 34692.07 49507.57 32812.76 49079.88 106998.09 98459.04 N-acetyl-L-tryptophan 83566.93 530202.19 107815.03 98458.74 157559.78 157496.55 204760.75 88811.98 78870.88 133078.48 224321.39 89668.59 305212.75 189318.8 292428.84 189772.08 Fructose 6-phosphate 47785.34 76821.95 21284.17 37632.68 41597.48 33719.92 25013.68 8992.58 44806.36 36299.49 30456.22 45396.88 42563.3 10995.25 11846.39 12309 Glucose 6-phosphate 200271.62 296741.16 78444.79 164376.45 149209.98 111375.15 89306.88 31555.79 181336 150877.94 105574.09 204367.58 142921.75 41936.84 44722.05 55730.64 Retinyl acetate 27299360 30862502 43508460 34551052 32907666 38829196 40793908 25487680 22685274 30390882 44482060 27517336 39823636 40602040 37562444 24236080 Betaine 150720336 179216256 99782936 110131288 110728552 69922464 70524712 70099368 69646440 48250060 69457424 66733348 78842072 44748132 48493872 60712924 Choline 147370800 166160112 124263832 132213336 133810240 115981672 121061016 73866552 162337472 176281328 176786432 186150976 195075408 124340280 151825152 128980000 Dimethylglycine 1195022.62 756287.25 792463.69 506627.09 793730.44 504416.09 814380.56 674655.5 89184.94 156687.56 80740.52 49871.41 98507.41 257124.2 157207.27 311295.91 Sarcosine 5447817.5 9784253 4712854 5537574 6089050.5 5449271.5 5720657.5 4096325.25 1759960.62 5382379.5 5980239.5 6162574.5 8724835 4933403.5 5275107.5 4462016 Hypotaurine 445451.59 673168 353752.75 472220.47 372704.66 189130.38 144556.77 57708.33 561820 370022.97 588793.81 430296.75 754978.5 312307.34 382263.03 161468.12 histamine 3169154.75 5855816 3027839 2826633.75 5420263.5 4082966 3236879.25 959138.69 5987428 7766994.5 8214120 5680303.5 5254596 1574457.38 1788937 2893475.75 Proline 13955353 25599598 16111199 15108997 15001525 15523283 16145757 13144595 13554392 11006251 23010054 16715611 27074522 16045376 19758994 13544016 Nicotinamide 617399.31 412715.97 317271.19 458289.34 359205.84 235049.83 241898.08 193939.62 508137.84 460594.53 298277.31 537373.94 384027.91 113466.9 83420.09 280587.41 pipecolinic acid 799967.06 672765.94 1258151.38 1236190.38 1139078.38 1397724.12 1512844.62 1405293.12 1101683.88 1418554.62 901813.19 1085887.38 731063.31 1180710.5 1377903.12 1218519.88 Creatine 106012136 144201872 96785320 110746616 123769112 82450088 88030256 68333064 99329720 110253344 98144536 130479320 122539072 101916288 90482952 79289912 Ornithine 3341446.25 4741349.5 4777923.5 3824204 5076536 4214786.5 4655151.5 3374824 4205984 4558202 4969500.5 3866601.75 5294449.5 4020388.25 8349463.5 3229451.75 Methylnicotinamide 4670454 4653474.5 5172454.5 3916905.25 3651681.75 3919757 4856942 2610734.25 4726591 5461704 3458699.75 4375447.5 3888247.75 1036054.06 1227400.38 2416399.25 Glutamine 98291584 107401848 130608808 117016344 114656800 110865416 110009624 115614752 125825208 112072256 125162104 115491168 127284736 124691136 135488688 118175008 Lysine 18452026 20544268 15759080 16174245 16060739 17177760 19185624 13198959 12217997 12066104 16627597 20534136 18532928 12008648 14469379 12242915 Methionine 8563359 10160408 8371868 8178636.5 10037107 7385199.5 7459894.5 4965178.5 6760910.5 6886573.5 7171918.5 8787399 9537373 4451615 6628265.5 5861588.5 Aminoadipate 635235.44 557904.44 341886.22 834053.31 586573.81 793784.19 776373.81 481151 332802.28 302704.91 309651.91 359676.75 317489.16 223475.12 234557.48 464186.09 Carnitine 52305268 70160168 60194028 73081480 84971208 54747212 54306524 59289772 43791592 35606128 26971446 44353688 59238528 53825920 57230076 38284832 3-methyl-histidine 5292108.5 4840495 5084724.5 5898708 6073996 4533777.5 5069550 4691736 6313647.5 5059519 5490427.5 5673378.5 6436666.5 3866795.25 4910011.5 4597200.5 Arginine 37676452 42205740 31345376 33878652 32471232 47751164 48367568 38399100 31385584 27224622 33819148 40646036 39239812 42884108 33651836 39217548 Guanidinosuccinic acid 13355.45 15512.74 72291.42 26838.04 27381.22 124989.22 157076.88 79087.8 31810.7 55064.11 9209.97 11504.95 16407.8 30610.94 58997.77 33785.46 Serotonin 1517730.62 1335014.88 22543.13 60734.66 2186004 2935835.75 1885422.62 1210387.88 1540770.62 452241.72 52667.75 69924.73 350418.09 1442370 1656690.88 572243.19 Glucosamine 114874.27 119202.91 122921.85 119170.62 145877.5 206951.75 230396.88 149344.25 94349.38 110068.97 80270.79 102570.3 100855.88 97076.87 86757.15 138528.48 N-Acetyl-lysine 168389.23 198581.98 194465.5 182846.2 177391.77 254401.19 336862 166788.33 139669.02 160247.98 164675.8 193976.83 156093.89 199277 225279.12 231861.89 Homoarginine 271147.62 283733.09 217674.23 217735.23 220974.17 265494.88 326193.16 249037.36 224776.61 168348.8 288710.34 299741.22 277128.66 307542.25 307593.78 220224.89 Trimethyllysine 2328641 2583701 1603392.38 2082804.62 1840091.62 2087562.38 2249503 1204762.5 2260182.75 1961643.62 1910091.62 2220417.25 2116901.75 1753538 1899850 1336865.5 Homocitrulline 142508.11 166894.2 147134.52 173658.31 178290.14 254821.14 377882.28 279575.56 195576.88 197087.11 211048.64 224038.23 187715.17 245579.23 366326.84 216447.92 Asymmetric dimethylarginine 2826467.25 2845963.75 2496689.5 2571312.75 2336250 3242323.25 3427217.25 2626524 2726652 2069893 3043317.75 3187665.25 2960823.25 3458387 3499669.25 2443514.75 O-Acetyl-L-carnitine 120797248 122173856 132054336 125398568 145886192 82264768 92214816 142757296 63685844 57791072 76142808 72948584 83078712 98008840 99912888 107782840 Kynurenine 37688.05 51711.38 36554.69 49628.21 44030.25 51925.86 73985.52 41648.58 51167.64 44597.14 35664.05 50274.07 46765.03 62116.14 75308.9 33724.72 Creatine Phosphate 729426.31 881678.5 408089.34 690623 715002.5 568276.31 443310.34 329107.16 436462.5 662185.94 804830.19 892792.75 731557.56 262244.72 263954.91 336773.72 gamma-glutamyl-alanine 93577.78 187714.33 94318.12 97104.84 109926.1 180664.05 208541.5 89679.25 86988.97 77889.4 123524.78 109678.25 161866.72 93543.2 109646.62 101142.99 Carnosine 187133.88 364087.5 91553.45 162246.81 169425.14 170232.89 150963.81 56235 212191.05 130079.69 145887.55 203951 205920.2 97255.03 101169.1 122710.63 Cystine 146348.95 70411.2 306980.38 291221.59 159466.33 375648.91 406165.91 523161.59 162474.28 148152.25 75259.54 209261.25 75611.65 91979.03 162674.94 594644.19 Anserine 268392.5 566759.5 176474.33 291799.97 278591.53 378515.34 364835 168810.31 331857.19 259532.39 227159.52 339327.28 324220.28 242855.12 266836.25 291556.72 Cytidine 191689.2 257195.64 173341.92 267418.72 198439.25 221158.3 175274.7 113269.4 227677.23 219647.5 195035.8 365528 327058.41 116901.71 221689.12 182825.52 Biotin 22240.51 23718.63 16948.75 30651.13 19449.33 21808 21802.64 6126.99 22414.17 16967.32 24732.06 33099.89 25330.79 10118.76 21826.44 15584.26 Glycerophosphocholine 4522842.5 4710216.5 4207365.5 4504584 5502453.5 2867660.75 2970874.75 2357174.75 3708396.75 2732833.75 3301790.75 4619270.5 4069051 763861.5 2644938.75 2312575 Adenosine 137399.55 79625.85 15439.94 15136.36 952890 3623669.25 872281.56 4386102.5 160702.38 12570.84 21089.24 139336.27 66883.9 517598.12 798269.69 743281.25 Glutaryl-carnitine 149746.06 302037.75 128447.25 193523.83 176143.19 103654.13 135889.38 118102.78 102324.62 88829.34 117509.34 119149.91 138485.44 147252.08 145866.83 126382.34 S-Adenosyl-homocysteine 45400.78 64298.14 14778.33 55837.22 84300.34 26409.11 21559.05 7557.05 84741.49 56470.96 17815.58 100599.34 58134.49 10172.01 105269.91 29222.75 S-Adenosylmethionine 68504.38 98438.34 46217.92 59143.56 70265.4 66342.7 75476.38 33090.95 76620.46 60357.72 49501.19 74789.3 63390.58 42337 50743.49 40208.21 Palmitoyl-Carnitine 400788 670618.69 336655.16 490090.41 370913.03 295703.81 235727.8 266978.5 365659.38 317194.78 452920.59 350436.97 467359.38 251901.75 449813.12 329934.97 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name PubChem KEGG Glycine 750 C00037 Pyruvate 1060 C00022 Alanine 602 C01401 Lactate 107689 C00186 Acetoacetate 96 C00164 N-Formylglycine 75606 - 3-Hydroxybutyric acid 441 C01089 3-hydroxyisobutyric acid 440873 C06001 Serine 5951 C00065 Glycerate 439194 C00258 Fumarate 444972 C00122 3-methyl-2-oxobutyrate 49 C00141 N-Acetylglycine 10972 - Guanidineacetic Acid 763 C00581 Valine 6287 C00183 Succinic acid 1110 C00042 Taurine 1123 C00245 Thymine 1135 C00178 Pyroglutamate 7405 C01879 N-Acetyl-L-alanine 88064 - trans-4-Hydroxy-L-proline 5810 C01157 Isoleucine 6306 C00407 Leucine 6106 C00123 Oxaloacetate 970 C00036 Ethylmalonic acid 11756 - 3-Ureidopropionic acid 111 C02642 Asparagine 6267 C00152 Aspartate 5960 C00049 Malate 222656 C00149 Urocanate 736715 C00785 O-Phosphoryethanolamine 1015 - 3-Methylglutaconate 1551553 - Alpha-Ketoglutarate 51 C00026 Glutamate 33032 C00025 N-Acetyl-serine 65249 - Citramalate 1081 C00815 Orotate 967 C00295 Dihydroorotic acid 648 - Allantoin 204 C02350 N-Methyl-L-glutamate 439377 C01046 3-Hydroxy-3-methylglutarate 1662 C03761 Fucose 17106 C01019 Phenylalanine 6140 C00079 Uric acid 1175 C00366 Dihydroxyacetone phosphate 668 C00111 Glycerol 3-phosphate 439162 C00093 N-Acetyl-Leucine 70912 - cis-aconitic acid 643757 C00417 N-Acetyl-aspartate 53630516 - Citrulline 9750 C00327 Hippuric acid 464 C01586 Glucose 5793 C00031 Tyrosine 6057 C00082 Homovanillic acid 1738 C05582 Galactitol 11850 C01697 Acetylglutamine 182230 - N-Acetyl-glutamate 70914 - Acetylmethionine 448580 C02712 Citrate 311 C00158 Glucuronic acid 444791 C00191 methyl beta-D-galactopyranoside 94214 - Gluconate 10690 C00257 Sebacic acid 5192 C08277 Tryptophan 6305 C00078 Indolelactate 676157 C02043 N-Acetyl-L-phenylalanine 74839 C03519 O-Succinyl-L-Homoserine 439406 - Pantothenate 6613 C00864 Ribose 5-phosphate 440101 C00117 Thymidine 5789 C00214 Uridine 6029 C00299 N-acetyl-L-tryptophan 700653 - Fructose 6-phosphate 69507 C00085 Glucose 6-phosphate 5958 C00092 Retinyl acetate 10245972 - Betaine 247 C00719 Choline 305 C00114 Dimethylglycine 673 C01026 Sarcosine 1088 C00213 Hypotaurine 107812 C00519 histamine 774 C00388 Proline 145742 C00148 Nicotinamide 936 C00153 pipecolinic acid 849 C00408 Creatine 586 C00300 Ornithine 6262 C00077 Methylnicotinamide 64950 - Glutamine 5961 C00064 Lysine 5962 C00047 Methionine 6137 C00073 Aminoadipate 92136 C00956 Carnitine 10917 C00487 3-methyl-histidine 64969 - Arginine 6322 C00062 Guanidinosuccinic acid 439918 C03139 Serotonin 5202 C00780 Glucosamine 439213 C00329 N-Acetyl-lysine 265949 - Homoarginine 9085 C01924 Trimethyllysine 440120 C03793 Homocitrulline 65072 C02427 Asymmetric dimethylarginine 123831 C03626 O-Acetyl-L-carnitine 7045767 C02571 Kynurenine 161166 C00328 Creatine Phosphate 587 C02305 gamma-glutamyl-alanine 440103 - Carnosine 439224 C00386 Cystine 67678 - Anserine 112072 C01262 Cytidine 6175 C00475 Biotin 171548 C00120 Glycerophosphocholine 657272 C00670 Adenosine 60961 C00212 Glutaryl-carnitine 71317118 - S-Adenosyl-homocysteine 439155 C00021 S-Adenosylmethionine 34756 C00019 Palmitoyl-Carnitine 461 - METABOLITES_END #END