#METABOLOMICS WORKBENCH zjj0326_20251011_042220 DATATRACK_ID:6553 STUDY_ID:ST004305 ANALYSIS_ID:AN007162 PROJECT_ID:PR002721 VERSION 1 CREATED_ON October 22, 2025, 6:29 pm #PROJECT PR:PROJECT_TITLE Lactate mitochondrial oxidation drives stemness potential in metastatic breast PR:PROJECT_TITLE cancer PR:PROJECT_SUMMARY Metastatic cancer cells, originating from cancer stem cells with metastatic PR:PROJECT_SUMMARY capacity, utilize nutrient flexibility to navigate the challenges of the PR:PROJECT_SUMMARY metastatic cascade. However, the nutrient required to maintain the stemness PR:PROJECT_SUMMARY potentials of metastatic cancer cells remains unclear. Here, we reveal that PR:PROJECT_SUMMARY metastatic breast cancer cells sustain stemness and initiate metastasis upon PR:PROJECT_SUMMARY detachment by taking up and oxidizing lactate. In detached metastasizing breast PR:PROJECT_SUMMARY cancer cells, lactate is incorporated into the tricarboxylic acid cycle, PR:PROJECT_SUMMARY boosting oxidative phosphorylation, and promoting the stemness potentials via PR:PROJECT_SUMMARY α-KG-DNMT3B-mediated SOX2 hypomethylation. Moreover, lactate is taken up and PR:PROJECT_SUMMARY oxidized in mitochondria by the CD147/MCT1/LDHB complex, which correlates with PR:PROJECT_SUMMARY stemness potentials and tumor metastasis in patients with breast cancer. An PR:PROJECT_SUMMARY intracellularly expressed single-chain variable fragment targeting mitochondrial PR:PROJECT_SUMMARY CD147 (mito-CD147 scFv) effectively disrupts the mitochondrial CD147/MCT1/LDHB PR:PROJECT_SUMMARY complex, inhibits lactate-induced stemness potential, depletes circulating PR:PROJECT_SUMMARY breast cancer cells, and reduces metastatic burden, suggesting promising PR:PROJECT_SUMMARY clinical applications in reducing lactate-fueled metastasis. PR:INSTITUTE Fourth Military Medical University PR:LAST_NAME Zhang PR:FIRST_NAME Jia-Jia PR:ADDRESS No. 169 Changle West Road, Xincheng District, Xi'an City, Shaanxi Province PR:EMAIL 1240568116@qq.com PR:PHONE +86 156 1927 6681 #STUDY ST:STUDY_TITLE Lactate mitochondrial oxidation drives stemness potential in metastatic breast ST:STUDY_TITLE cancer ST:STUDY_SUMMARY Metastatic cancer cells, originating from cancer stem cells with metastatic ST:STUDY_SUMMARY capacity, utilize nutrient flexibility to navigate the challenges of the ST:STUDY_SUMMARY metastatic cascade. However, the nutrient required to maintain the stemness ST:STUDY_SUMMARY potentials of metastatic cancer cells remains unclear. Here, we reveal that ST:STUDY_SUMMARY metastatic breast cancer cells sustain stemness and initiate metastasis upon ST:STUDY_SUMMARY detachment by taking up and oxidizing lactate. In detached metastasizing breast ST:STUDY_SUMMARY cancer cells, lactate is incorporated into the tricarboxylic acid cycle, ST:STUDY_SUMMARY boosting oxidative phosphorylation, and promoting the stemness potentials via ST:STUDY_SUMMARY α-KG-DNMT3B-mediated SOX2 hypomethylation. Moreover, lactate is taken up and ST:STUDY_SUMMARY oxidized in mitochondria by the CD147/MCT1/LDHB complex, which correlates with ST:STUDY_SUMMARY stemness potentials and tumor metastasis in patients with breast cancer. An ST:STUDY_SUMMARY intracellularly expressed single-chain variable fragment targeting mitochondrial ST:STUDY_SUMMARY CD147 (mito-CD147 scFv) effectively disrupts the mitochondrial CD147/MCT1/LDHB ST:STUDY_SUMMARY complex, inhibits lactate-induced stemness potential, depletes circulating ST:STUDY_SUMMARY breast cancer cells, and reduces metastatic burden, suggesting promising ST:STUDY_SUMMARY clinical applications in reducing lactate-fueled metastasis. ST:INSTITUTE Fourth Military Medical University ST:LAST_NAME Zhang ST:FIRST_NAME Jia-Jia ST:ADDRESS No. 169 Changle West Road, Xincheng District, Xi'an City, Shaanxi Province ST:EMAIL 1240568116@qq.com ST:PHONE 15619276681 #SUBJECT SU:SUBJECT_TYPE Cultured cells SU:SUBJECT_SPECIES Homo sapiens SU:TAXONOMY_ID 9606 SU:GENOTYPE_STRAIN Wild type SU:AGE_OR_AGE_RANGE NA SU:WEIGHT_OR_WEIGHT_RANGE NA SU:HEIGHT_OR_HEIGHT_RANGE NA SU:GENDER Female SU:CELL_BIOSOURCE_OR_SUPPLIER ATCC SU:CELL_STRAIN_DETAILS MCF7 SU:SUBJECT_COMMENTS NA SU:CELL_PRIMARY_IMMORTALIZED No. SU:CELL_PASSAGE_NUMBER 2 SU:CELL_COUNTS 1x10e6 SU:SPECIES_GROUP human #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 - M_Ad_1_1 Adherent:Adherent | Sample source:MCF-7 breast cancer cell line RAW_FILE_NAME=M_Ad_1_1.cdf SUBJECT_SAMPLE_FACTORS - M_Ad_2_1 Adherent:Adherent | Sample source:MCF-7 breast cancer cell line RAW_FILE_NAME=M_Ad_2_1.cdf SUBJECT_SAMPLE_FACTORS - M_Ad_3_1 Adherent:Adherent | Sample source:MCF-7 breast cancer cell line RAW_FILE_NAME=M_Ad_3_1.cdf SUBJECT_SAMPLE_FACTORS - M_Ad_4_1 Adherent:Adherent | Sample source:MCF-7 breast cancer cell line RAW_FILE_NAME=M_Ad_4_1.cdf SUBJECT_SAMPLE_FACTORS - M_Ad_5_1 Adherent:Adherent | Sample source:MCF-7 breast cancer cell line RAW_FILE_NAME=M_Ad_5_1.cdf SUBJECT_SAMPLE_FACTORS - M_Ad_6_1 Adherent:Adherent | Sample source:MCF-7 breast cancer cell line RAW_FILE_NAME=M_Ad_6_1.cdf SUBJECT_SAMPLE_FACTORS - M_AR_1_1 Adherent:anoikis-resistant | Sample source:MCF-7 breast cancer cell line RAW_FILE_NAME=M_AR_1_1.cdf SUBJECT_SAMPLE_FACTORS - M_AR_2_1 Adherent:anoikis-resistant | Sample source:MCF-7 breast cancer cell line RAW_FILE_NAME=M_AR_2_1.cdf SUBJECT_SAMPLE_FACTORS - M_AR_3_1 Adherent:anoikis-resistant | Sample source:MCF-7 breast cancer cell line RAW_FILE_NAME=M_AR_3_1.cdf SUBJECT_SAMPLE_FACTORS - M_AR_4_1 Adherent:anoikis-resistant | Sample source:MCF-7 breast cancer cell line RAW_FILE_NAME=M_AR_4_1.cdf SUBJECT_SAMPLE_FACTORS - M_AR_5_1 Adherent:anoikis-resistant | Sample source:MCF-7 breast cancer cell line RAW_FILE_NAME=M_AR_5_1.cdf SUBJECT_SAMPLE_FACTORS - M_AR_6_1 Adherent:anoikis-resistant | Sample source:MCF-7 breast cancer cell line RAW_FILE_NAME=M_AR_6_1.cdf #COLLECTION CO:COLLECTION_SUMMARY Supernatants from 1×10e6 MCF7 AR and Ad cells (n=6 biological replicates) were CO:COLLECTION_SUMMARY collected and centrifuged at 3000×g for 10 min at 4 ℃ to remove cell debris CO:COLLECTION_SUMMARY and the lipid layer. CO:SAMPLE_TYPE Cell culture supernatant CO:COLLECTION_METHOD Direct collection CO:COLLECTION_FREQUENCY One time collection CO:COLLECTION_DURATION About 20 min. CO:VOLUMEORAMOUNT_COLLECTED 1 ml CO:STORAGE_CONDITIONS -80℃ #TREATMENT TR:TREATMENT_SUMMARY MCF7, cells were cultured in RPMI 1640 medium with 3.15g/L glucose. All cells TR:TREATMENT_SUMMARY were routinely supplemented with 10% fetal bovine serum (FBS), 1% TR:TREATMENT_SUMMARY penicillin/streptomycin, and 2% L-glutamine. Cells surviving for 7 days in TR:TREATMENT_SUMMARY glucose-containing medium (3.15g/L) under detached suspension culture conditions TR:TREATMENT_SUMMARY in ultra-low attachment plates were considered anoikis-resistant (AR) cells, TR:TREATMENT_SUMMARY while cells cultured in uncoated common plates under attached conditions with TR:TREATMENT_SUMMARY glucose-containing medium (3.15g/L) served as control adherent (Ad) cells. TR:TREATMENT Adherent (Ad) cells and anoikis-resistant (AR) cells. TR:CELL_STORAGE 37℃ TR:CELL_GROWTH_CONTAINER 6-well plate TR:CELL_GROWTH_CONFIG MCF7 cells were cultured in RPMI 1640 medium with 3.15g/L glucose. All cells TR:CELL_GROWTH_CONFIG were routinely supplemented with 10% fetal bovine serum (FBS), 1% TR:CELL_GROWTH_CONFIG penicillin/streptomycin, and 2% L-glutamine. TR:CELL_MEDIA RPMI 1640 medium TR:CELL_ENVIR_COND 37℃, 5% CO2 TR:CELL_HARVESTING Collect the supernatant TR:CELL_PCT_CONFLUENCE 90% TR:CELL_MEDIA_LASTCHANGED Change the medium every three days。 #SAMPLEPREP SP:SAMPLEPREP_SUMMARY The medium samples were thawed on ice-bath and centrifuged for 5 min at 4 °C SP:SAMPLEPREP_SUMMARY and 3000g (Microfuge 20R， Beckman Coulter, Inc., Indianapolis, IN, USA) to SP:SAMPLEPREP_SUMMARY separate debris or a lipid layer. Each aliquot of 50 μL sample was mixed with SP:SAMPLEPREP_SUMMARY 10 μL of internal standard, to which 175 μL of pre-chilled methanol/chloroform SP:SAMPLEPREP_SUMMARY (v/v=3/1) was added. After centrifugation at 14,000 g and 4 °C for 20 min SP:SAMPLEPREP_SUMMARY (Microfuge 20R，Beckman Coulter, Inc., Indianapolis, IN, USA), each 200 μL of SP:SAMPLEPREP_SUMMARY the supernatant was carefully transferred to an autosampler vial (Agilent SP:SAMPLEPREP_SUMMARY Technologies, Foster City, CA, USA). The remaining supernatant from each sample SP:SAMPLEPREP_SUMMARY was pooled to make quality control samples. All the samples in autosampler vials SP:SAMPLEPREP_SUMMARY were evaporated briefly to remove chloroform using a CentriVap vacuum SP:SAMPLEPREP_SUMMARY concentrator (Labconco, Kansas City, MO, USA), and further lyophilized with a SP:SAMPLEPREP_SUMMARY FreeZone freeze dryer equipped with a stopping tray dryer (Labconco, Kansas SP:SAMPLEPREP_SUMMARY City, MO, USA). The sample derivatization and injection were performed by a SP:SAMPLEPREP_SUMMARY robotic multipurpose sample MPS2 with dual heads (Gerstel, Muehlheim, Germany). SP:SAMPLEPREP_SUMMARY Briefly, the dried sample was derivatized with 50 μL of methoxyamine (20 mg/mL SP:SAMPLEPREP_SUMMARY in pyridine) at 30°C for 2 hr, followed by the addition of 50 μL of MSTFA (1% SP:SAMPLEPREP_SUMMARY TMCS) containing FAMEs as retention indices at 37.5 °C for another 1 hr using SP:SAMPLEPREP_SUMMARY the sample preparation head. In parallel, the derivatized samples were injected SP:SAMPLEPREP_SUMMARY with sample injection head after derivatization. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY A time-of-flight mass spectrometry (GC-TOF/MS) system (Pegasus HT, Leco Corp., CH:CHROMATOGRAPHY_SUMMARY St. Joseph, MO,USA) with an Agilent 7890B gas chromatography and a Gerstel CH:CHROMATOGRAPHY_SUMMARY multipurpose sample MPS2 with dual heads (Gerstel, Muehlheim, Germany). A Rxi-5 CH:CHROMATOGRAPHY_SUMMARY ms capillary column (30m×250μm i.d., 0.25-μm film thickness; Restek CH:CHROMATOGRAPHY_SUMMARY corporation, Bellefonte, PA, USA) was used for separation. Helium was used as CH:CHROMATOGRAPHY_SUMMARY the carrier gas at a constant flow rate of 1.0 mL/min. The temperature of CH:CHROMATOGRAPHY_SUMMARY injection and transfer interface were both set to 270 °C. The source CH:CHROMATOGRAPHY_SUMMARY temperature was 220 °C. The measurements were made using electron impact CH:CHROMATOGRAPHY_SUMMARY ionization (70 eV) in the full scan mode (m/z 50-500). CH:CHROMATOGRAPHY_TYPE GC CH:INSTRUMENT_NAME Agilent 7890B CH:COLUMN_NAME Restek Rtx-5Sil MS (30m x 0.25mm, 0.25um) CH:SOLVENT_A NA CH:SOLVENT_B NA CH:FLOW_GRADIENT NA CH:FLOW_RATE 1.0 mL/min CH:COLUMN_TEMPERATURE 270 °C #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Leco Pegasus HT TOF MS:INSTRUMENT_TYPE TOF MS:MS_TYPE EI MS:ION_MODE POSITIVE MS:MS_COMMENTS Metabolite Annotation Metabolite annotation was performed by comparing the MS:MS_COMMENTS retention indices and mass spectral data withthose previously generated from MS:MS_COMMENTS reference standards of known structures present in JiaLib metabolite database MS:MS_COMMENTS using ChromaTOF software . The current JiaLib comprises over 1,200 mammalian MS:MS_COMMENTS metabolites with15-year accumulation and is one of the most comprehensive MS:MS_COMMENTS metabolite libraries in the world. The referencechemicals present in JiaLib were MS:MS_COMMENTS commercially purchased from Sigma-Aldrich (St. Louis, MO, USA), Santa Cruz MS:MS_COMMENTS (Dallas, TX, USA), Nu-Chek Prep (Elysian, MN, USA), and synthesized in the MS:MS_COMMENTS laboratory.Commercial libraries such as NIST library 2014 and LECO/Fiehn MS:MS_COMMENTS Metabolomics Library for GC-TOF/MS are NOT recommended for precise metabolite MS:MS_COMMENTS annotation for the following two reasons: 1) neither instrument vendor’s MS:MS_COMMENTS software nor commercially available software can annotate metabolites using both MS:MS_COMMENTS retention indices and mass spectral data; and 2) both NIST and Fiehn libraries MS:MS_COMMENTS contain a large portion of reference materials that are intended for chemical MS:MS_COMMENTS annotation in food, plant, drug, and synthesized chemistry. Data Analysis and MS:MS_COMMENTS Software The raw data generated by GC-TOF/MS were processed using ChromaTOF MS:MS_COMMENTS (v4.71, Leco Corp., St.Joseph, MO,USA) for automated baseline denosing and MS:MS_COMMENTS smoothing, peak picking, deconvolution and peak alignment. Compound MS:MS_COMMENTS identification was performed by comparing both MS similarity and FAMEs retention MS:MS_COMMENTS index distance with the referenced standards in one of the most extensive MS:MS_COMMENTS metabolite database – JiaLib in the world. The self-developed platform MS:MS_COMMENTS iMAP（v1.0, Metabo-Profile, Shanghai, China）was used for subsequent MS:MS_COMMENTS statistical analyses, including PCA, OPLS-DA, univariate analysis and pathway MS:MS_COMMENTS analysis, et al. Statistics Our proprietary software can perform a collection of MS:MS_COMMENTS data processing, interpretation, and visualization. For many metabolomics MS:MS_COMMENTS studies, two types of statistical analysis are extensively performed: 1) MS:MS_COMMENTS multivariate statistical analyses such as principal component analysis (PCA), MS:MS_COMMENTS partial least square discriminant analysis (PLS-DA), orthogonal partial least MS:MS_COMMENTS square discriminant analysis (OPLS-DA), random forest, support vector machine MS:MS_COMMENTS learning and so on; 2) univariate statistical analyses including student t-test, MS:MS_COMMENTS Mann-Whitney-Wilcoxon (U-test), ANOVA, correlation analysis, etc. Statistical MS:MS_COMMENTS algorithms are adapted from the widely used statistical analysis software MS:MS_COMMENTS packages in R studio (http://cran.r-project.org/). The optimal choice of MS:MS_COMMENTS statistical methods is often driven by the data and the project goals. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS z-score MS_METABOLITE_DATA_START Samples M_Ad_1_1 M_Ad_2_1 M_Ad_3_1 M_Ad_4_1 M_Ad_5_1 M_Ad_6_1 M_AR_1_1 M_AR_2_1 M_AR_3_1 M_AR_4_1 M_AR_5_1 M_AR_6_1 Factors Adherent:Adherent | Sample source:MCF-7 breast cancer cell line Adherent:Adherent | Sample source:MCF-7 breast cancer cell line Adherent:Adherent | Sample source:MCF-7 breast cancer cell line Adherent:Adherent | Sample source:MCF-7 breast cancer cell line Adherent:Adherent | Sample source:MCF-7 breast cancer cell line Adherent:Adherent | Sample source:MCF-7 breast cancer cell line Adherent:anoikis-resistant | Sample source:MCF-7 breast cancer cell line Adherent:anoikis-resistant | Sample source:MCF-7 breast cancer cell line Adherent:anoikis-resistant | Sample source:MCF-7 breast cancer cell line Adherent:anoikis-resistant | Sample source:MCF-7 breast cancer cell line Adherent:anoikis-resistant | Sample source:MCF-7 breast cancer cell line Adherent:anoikis-resistant | Sample source:MCF-7 breast cancer cell line 2-Hydroxy-3-methylpentanoic acid 0.63223204724243 0.812964328917271 1.02282775255651 0.919731150436177 0.575449335252727 1.45786444601304 -0.921996872 -1.622160271 -0.561047604 -0.788320865 -0.707300109 -0.820243339 2-Hydroxyvaleric acid -0.610235801 -0.911074803 -0.335754357 -0.786438808 -0.640642189 -1.02971343 0.372120805297585 2.59583079275239 0.462760133845741 0.181639088019582 0.0148989671567476 0.68660960074752 2-Phenylacetamide -0.514725872 -0.367478348 -0.751528062 -0.709393138 -1.551142954 -0.651035531 -0.275384447 0.468274671981645 1.57845312378398 0.867704987123847 0.132870798175409 1.77338477032505 2-Pyrrolidinone 0.955524968241361 1.74708887218923 1.1256513565244 0.719182096811019 0.266571781185919 0.570525588330474 -0.867215585 -0.917679048 -0.974255244 -0.887964253 -0.789359261 -0.948071273 3-Amino-2-piperidone 0.230667064102463 0.782577073181906 -1.585454343 -1.383846423 -0.820648501 -1.041000241 0.235786180473103 0.633083993245398 1.00153990944998 -0.246034468 1.43070877003213 0.762620986291325 3-Hydroxybutyric acid -0.870498467 0.0642023962699115 -0.940591928 -1.366193185 0.860883270201912 -1.872337484 0.593349635112998 1.1062348367775 0.749815055835146 0.500886194599557 0.871541582460272 0.302708091979625 Adenine 1.26104322309913 1.09646563257846 1.00751545345287 1.02670140718885 0.733652913055448 0.500181771234515 -1.023007584 -1.019569787 -0.731348834 -0.994933298 -1.016105713 -0.840595184 Alanine 1.06039105513322 0.0591180287126405 1.04243893213282 0.861452781574586 0.954271382346636 1.44826800501254 -0.763429227 -1.104779054 -0.896703261 -0.675813478 -1.00811238 -0.977102785 Aminomalonic acid -0.445769205 -0.955753337 -1.093941214 -1.09699219 -0.65921577 -1.067069017 0.713543191130644 0.042026340479093 0.842149480262445 1.35387941952669 1.01075948144007 1.35638281984226 Arginine -0.916281095 0.157594631562921 -1.041521024 -0.685899542 -1.241915175 -0.904289467 0.509738748933276 0.420627784304616 1.1126148939367 0.330574863171932 2.10028834986778 0.15846703131355 Asparagine -0.856234255 -0.960784297 -0.930632444 -0.957981427 -0.905436184 -1.004859876 0.498961017670683 0.923746824979371 1.35541242424404 0.766449423820141 0.864987065533624 1.20637172713549 Benzoic acid 0.0786209721510917 0.800531214146014 0.951074690328768 1.12182909157104 0.614389892253057 1.47648831355801 -0.677769209 0.165333973614971 -1.156932413 -1.132323821 -1.202754059 -1.038488645 beta-Alanine 1.32222922982213 0.988682601094423 0.997750048057596 0.708306007199051 1.01219744788908 0.625784484950031 -0.927183898 -0.827373577 -0.90723807 -0.999074197 -1.057203418 -0.936876658 Capric acid -0.531945894 -1.078247168 -0.979677272 -1.173540652 -0.529490248 -1.189026228 1.03904661584854 0.583072435328356 1.10866082808582 0.767951682906037 0.592658636691244 1.39053726395252 Caprylic acid -1.011686704 -1.044566865 -0.762845455 -0.78900295 -0.944811144 -0.77410649 0.45066181455081 1.94044517116955 0.883710205659456 0.541606793160608 0.703589364140827 0.807006260295553 Cellobiose -0.731916546 -0.794554182 -0.807462965 -0.928050628 -1.179452584 -0.974278651 0.222550087038032 0.954308529994405 1.44549012401174 0.463941184361567 1.19071094611508 1.13871468524715 Cholesterol 1.19265884728092 1.12261761210037 0.998696540620327 0.0738159993750221 0.951733260239859 0.953666225050946 -1.227244028 -0.589375976 -0.811702898 -1.513350257 -0.446144375 -0.705370951 Cysteine 0.0547096585363394 2.08579321865936 0.136650216963529 0.30966866458874 0.0633901124835255 1.26981196777348 -0.92834858 -0.070698971 -0.802053685 -1.257505355 0.421642741144162 -1.283059989 Cystine -0.707744734 -0.832053899 -0.938774715 -0.961600262 -0.906705238 -0.947943071 0.458483110534708 1.15590600735422 1.45039320317005 0.523069940858503 0.182791365883819 1.52417829169715 Erythritol 2.31847143880369 0.699715801813635 0.739375027708388 0.332613033864252 0.174593985059901 0.455358299013203 -1.132168404 -0.940733192 -0.489195809 -0.93793832 -0.933936145 -0.286155717 Ethanolamine -0.48622845 0.270966394493791 1.55961346426671 1.33491665062099 0.721103854820972 0.84386231288775 -1.134264083 0.253253251401646 -0.328677773 -0.332602413 -1.241258581 -1.460684629 Fructose-1-phosphate -0.693650079 -0.424238332 -0.589494616 -0.611653495 -0.565695007 -0.451256838 -0.434015089 0.238663945433459 0.077683403590341 0.255977590224775 2.95237927791213 0.245299238308523 Glucosamine-1P -0.581926616 -0.738410436 -0.551277073 -0.852591504 -1.081823373 -1.226565739 0.152968676631006 1.46859275298065 1.31192397823358 -0.126959061 1.02537014608324 1.20069824777558 Glucose 6-phosphate -0.813552262 -0.726051827 -0.581579337 -0.815664958 -1.226012943 -0.982329257 0.411757893667678 1.36587870941947 0.864055583497514 0.417036250663703 1.82008899692939 0.266373148905252 Glutamic acid 1.2048765830998 1.02952558381511 0.997413319706718 0.906093838780437 0.623905188195263 0.934442511095562 -0.974402212 -0.947260328 -0.940025892 -0.975212678 -0.926747688 -0.932608228 Glutamine 0.0334631502884895 -0.471244603 -0.665374242 -1.073716645 -1.427832568 -1.015528725 -0.208594845 0.805646690962209 1.61863956223008 0.0720526222402557 0.974938617055675 1.3575509840897 Glutamylvaline -0.822442113 -0.836699081 -0.921669448 -1.201073449 -0.715124734 -0.296857496 0.591069908437126 2.19363579624065 1.11211194835353 0.507947256264786 0.190142795239594 0.198958617054779 Glyceric acid 0.0354854554435398 0.597839305355798 1.31278779619324 1.29611477287793 0.537194135402089 1.49115774498512 -0.964287098 -0.71231567 -0.868228056 -1.008945936 -1.005258774 -0.711543677 Glycerol-3-galactoside -0.787621101 -0.637703981 -0.840323396 -0.782193581 -0.697875081 -0.832491708 2.12975208344429 0.251096027579178 1.64332081978145 -0.024415572 0.35105972495464 0.227395764293266 Histidine -0.995015665 -0.136863602 -0.869564966 -0.738302278 -0.773031696 -0.663234921 1.82617756085389 0.231565319736118 0.00881094272852677 0.460792732261423 1.98461662316041 -0.33595005 Homocysteine -1.485862133 -0.363377651 -0.239702873 -0.566040151 -0.929897787 -1.140173129 0.420298188151224 0.721754342577658 2.1037103741807 0.0910889643392316 0.587846057076847 0.80035579800135 Hydroxypropionic acid -1.025723092 -0.5930466 -0.747279334 -1.010398288 -1.021864158 -1.188431769 0.644300760025081 0.752491013559746 1.0727700420457 0.698559437771648 1.29656674738011 1.12205524006479 Lactic acid 0.882412098138276 0.944563194048199 0.797028200837468 0.528461491493725 1.71087028200999 0.640783708929921 -0.813885176 -1.004459178 -0.881434149 -0.86775737 -0.983935857 -0.952647245 Lactose -0.799619495 -0.781397752 -0.738402356 -0.89646726 -1.263902131 -0.951423821 0.165377438980915 1.15969185038177 1.30608989695803 0.561986163878137 1.12501738098585 1.11305008289696 Malic acid 2.68263428228879 0.403487664360818 0.278362588274319 0.222619231417167 0.68922536049968 -0.348050683 -0.871670055 -0.716698981 -0.400079278 -0.955732725 -0.699746378 -0.284351027 Malonic acid 0.759362685774353 0.505155357486242 1.11502296049053 0.368787361857608 1.82391125796011 0.105715168457426 -0.80636328 0.419229151112854 -0.95596636 -1.134188812 -1.141460695 -1.059204797 Maltol -1.062804513 -0.866681397 -0.591206031 -0.682541971 -1.002635918 -0.862022158 -0.00783665 1.73496070838566 0.885805727595949 0.207628102569506 0.813510429885592 1.43382366977783 Maltose -0.592578901 -0.817198877 -0.995598611 -1.064936379 -1.095098832 -1.036452724 0.729606360229736 0.798176285850302 1.01756041971088 0.621907510222514 1.33343916285718 1.10117458617046 Melissic acid 0.321807897392965 -1.580911165 -0.738655163 -1.284464291 -0.58262539 0.454428648664686 1.49481985843047 0.662740480667701 -0.938060246 0.158802920596038 1.0938608032161 0.938255645560336 Methionine 0.575584792963797 -0.214510929 -1.163666553 -1.314193709 -1.152101801 -0.793457341 -0.127257421 0.984181606759674 1.01560533337297 -0.414360596 1.24858859852943 1.35558801795863 Methionine sulfoxide -0.644912135 -1.376836272 0.0906941237400078 0.0105627547394713 -0.955467727 -1.744408846 0.453979040662961 0.344824956788084 1.41194294746715 0.683530484754252 0.389389400596553 1.33670127110539 Methylcysteine 0.887986245716481 1.06746397814509 1.19792475879452 1.02505137840643 0.312766271252657 1.06556677384905 -0.723800347 -0.999347577 -1.279962402 -0.9583852 -0.773446722 -0.82181716 Niacinamide -0.955331437 -0.959199807 -0.946443157 -0.954623893 -0.915582797 -0.961036635 0.84013577147311 0.862476294229377 1.15844816086234 0.700619627156744 0.913325544264536 1.21721232801664 Nicotinic acid 0.862790080746403 0.928285779291057 1.06862955582721 0.986191046938428 0.805778707285709 1.07690782676833 -0.967481635 -0.967743423 -0.95440044 -0.960648942 -0.943087059 -0.935221497 Ornithine 1.4899529090204 0.693034047544564 1.22565980499654 1.08702506741418 0.140121105424474 0.494687495102089 -1.034249226 0.0267755738600749 -0.915930518 -1.146935552 -0.981795582 -1.078345124 Phosphate 0.305798888583564 0.38219920733439 1.36285452310131 1.35091296158293 1.25359176766054 0.728731200361958 -0.749974681 -0.687004059 -0.923838614 -0.845045813 -1.064809136 -1.113416247 Proline -0.459950027 0.756078055917169 1.21274426944992 1.27346772096497 0.41407315658719 1.64374953028458 -1.154087708 -0.508444006 -0.617646602 -1.063617858 -0.86691349 -0.629453042 Pyroglutamic acid -0.396578209 -0.86148918 -1.020605483 -1.219759711 -0.621682005 -1.331959029 1.30290605636567 0.878163493010808 1.09212147253664 1.02913725335671 0.454531168537429 0.695214174160612 Pyruvic acid 1.95849356099781 0.392185398529963 0.658423284698158 0.205843711529446 1.52649340561819 -0.188225822 -1.197665852 -1.124905324 -0.227183509 -0.820385661 -0.741032587 -0.442040607 Ribose 5-phosphate 0.225337574007623 0.105370518021354 -1.133962782 -1.211321382 -0.738859332 -1.165821337 1.36625945523628 1.07011001398277 1.02136051739225 1.00310296078917 -1.002925677 0.461349471471017 Serine -0.796407721 -0.983194571 -0.913868977 -0.951054817 -1.080222347 -0.936628158 0.727203832346945 0.805423272334758 1.10968786720679 0.671904449353261 1.16173418904557 1.18542298021916 Sorbitol 1.83829175484464 0.93477811846547 0.246187157789301 0.180008014475067 0.324185492306635 0.797832004394237 0.148317650194089 -0.919144246 -1.357789981 -1.131907164 0.293633282078514 -1.354392082 Succinimide 0.919031211001671 1.76352259222323 1.12218647942399 0.765660470530539 0.260135070886427 0.537323641546453 -0.878115684 -0.843400906 -1.012430591 -0.901613308 -0.759660229 -0.972638748 Threonic acid 2.0933412718325 0.897099881429205 0.66861618114828 0.63825609240881 0.528472872640214 0.287402697441174 -0.729888117 -0.67527101 -0.743179966 -1.27551411 -0.875682237 -0.813653557 Tyrosine -0.290285269 0.202707245273082 -0.676432853 -0.709038812 -0.985256235 -0.961109266 0.137313367923265 1.07365656246546 0.784952678897686 -1.311234718 1.98923126306545 0.745496034747181 Uracil -1.547259618 -1.291124298 -0.367623329 -0.455083289 -1.027157076 0.0107249932558672 0.376167611858128 0.9367356804446 1.55770165677959 -0.046102761 0.492233087526551 1.36078734157194 Valine -0.4609276 0.630047753735494 1.22965210572341 0.872826006436255 1.14532054403494 1.1204797349073 -0.616436849 -2.035345466 -0.457066276 -0.723358636 -0.20085278 -0.504338537 Vanillin 0.272611390118295 0.630973505959179 0.974899550129985 0.973890254316023 1.65649051750576 0.831773910259198 -0.470227191 -0.99987711 -1.157738882 -0.612827097 -0.890083464 -1.209885384 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name HMDB KEGG Pathway 2-Hydroxy-3-methylpentanoic acid HMDB0000317 NA NA 2-Hydroxyvaleric acid HMDB0001863 NA NA 2-Phenylacetamide HMDB0010715 C02505 Phenylalanine metabolism 2-Pyrrolidinone HMDB0002039 C11118 NA 3-Amino-2-piperidone HMDB0000323 NA NA 3-Hydroxybutyric acid HMDB0000357 C01089 Butanoate metabolism;Synthesis and degradation of ketone bodies Adenine HMDB0000034 C00147 Purine metabolism Alanine HMDB0000161 C00041 Alanine, aspartate and glutamate metabolism;Aminoacyl-tRNA biosynthesis;Cysteine and methionine metabolism;Selenoamino acid metabolism;Taurine and hypotaurine metabolism Aminomalonic acid HMDB0001147 C00872 NA Arginine HMDB0000517 C00062 Aminoacyl-tRNA biosynthesis;Arginine and proline metabolism;D-Arginine and D-ornithine metabolism Asparagine HMDB0000168 C00152 Alanine, aspartate and glutamate metabolism;Aminoacyl-tRNA biosynthesis;Cyanoamino acid metabolism;Nitrogen metabolism Benzoic acid HMDB0001870 C00180 Phenylalanine metabolism beta-Alanine HMDB0000056 C00099 beta-Alanine metabolism;Pantothenate and CoA biosynthesis;Propanoate metabolism;Pyrimidine metabolism Capric acid HMDB0000511 C01571 Fatty acid biosynthesis Caprylic acid HMDB0000482 C06423 Fatty acid biosynthesis Cellobiose HMDB0000055 C06422 NA Cholesterol HMDB0000067 C00187 Primary bile acid biosynthesis;Steroid hormone biosynthesis Cysteine HMDB0000574 C00097 Aminoacyl-tRNA biosynthesis;Cysteine and methionine metabolism;Glutathione metabolism;Glycine, serine and threonine metabolism;Pantothenate and CoA biosynthesis;Sulfur metabolism;Taurine and hypotaurine metabolism;Thiamine metabolism Cystine HMDB0000192 C00491 Cysteine and methionine metabolism Erythritol HMDB0002994 C00503 NA Ethanolamine HMDB0000149 C00189 Glycerophospholipid metabolism Fructose-1-phosphate HMDB0001076 C01094 Fructose and mannose metabolism Glucosamine-1P HMDB0001109 NA NA Glucose 6-phosphate HMDB0001401 C00092 NA Glutamic acid HMDB0000148 C00025 Alanine, aspartate and glutamate metabolism;Aminoacyl-tRNA biosynthesis;Arginine and proline metabolism;Butanoate metabolism;D-Glutamine and D-glutamate metabolism;Glutathione metabolism;Histidine metabolism;Nitrogen metabolism;Porphyrin and chlorophyll metabolism Glutamine HMDB0000641 C00064 Alanine, aspartate and glutamate metabolism;Aminoacyl-tRNA biosynthesis;Arginine and proline metabolism;D-Glutamine and D-glutamate metabolism;Nitrogen metabolism;Purine metabolism;Pyrimidine metabolism Glutamylvaline HMDB0028832 NA NA Glyceric acid HMDB0000139 C00258 Glycerolipid metabolism;Glycine, serine and threonine metabolism;Glyoxylate and dicarboxylate metabolism;Pentose phosphate pathway Glycerol-3-galactoside NA NA NA Histidine HMDB0000177 C00135 Aminoacyl-tRNA biosynthesis;beta-Alanine metabolism;Histidine metabolism;Nitrogen metabolism Homocysteine HMDB0000742 C00155 Cysteine and methionine metabolism;Nitrogen metabolism;Sulfur metabolism Hydroxypropionic acid HMDB0000700 C01013 beta-Alanine metabolism;Propanoate metabolism Lactic acid HMDB0000190 C00186 Glycolysis or Gluconeogenesis;Propanoate metabolism;Pyruvate metabolism Lactose HMDB0000186 C00243 Galactose metabolism Malic acid HMDB0000156 C00149 Citrate cycle (TCA cycle);Glyoxylate and dicarboxylate metabolism;Pyruvate metabolism Malonic acid HMDB0000691 C00383 beta-Alanine metabolism;Pyrimidine metabolism Maltol HMDB30776 C11918 NA Maltose HMDB0000163 C00208 Starch and sucrose metabolism Melissic acid HMDB0030925 NA NA Methionine HMDB0000696 C00073 Aminoacyl-tRNA biosynthesis;Cysteine and methionine metabolism Methionine sulfoxide HMDB0002005 C02989 Cysteine and methionine metabolism Methylcysteine HMDB0002108 NA NA Niacinamide HMDB0001406 C00153 Nicotinate and nicotinamide metabolism Nicotinic acid HMDB0001488 C00253 Nicotinate and nicotinamide metabolism Ornithine HMDB0000214 C00077 Arginine and proline metabolism;D-Arginine and D-ornithine metabolism;Glutathione metabolism Phosphate HMDB0001429 C00009 NA Proline HMDB0000162 C00148 Aminoacyl-tRNA biosynthesis;Arginine and proline metabolism Pyroglutamic acid HMDB0000267 C01879 Glutathione metabolism Pyruvic acid HMDB0000243 C00022 Alanine, aspartate and glutamate metabolism;Arginine and proline metabolism;Ascorbate and aldarate metabolism;Butanoate metabolism;Citrate cycle (TCA cycle);Cysteine and methionine metabolism;Glycine, serine and threonine metabolism;Glycolysis or Gluconeogenesis;Glyoxylate and dicarboxylate metabolism;Nicotinate and nicotinamide metabolism;Pantothenate and CoA biosynthesis;Pentose and glucuronate interconversions;Pentose phosphate pathway;Phenylalanine metabolism;Pyruvate metabolism;Taurine and hypotaurine metabolism;Terpenoid backbone biosynthesis;Tyrosine metabolism;Valine, leucine and isoleucine biosynthesis;Vitamin B6 metabolism Ribose 5-phosphate HMDB0001548 C00117 Pentose phosphate pathway;Purine metabolism Serine HMDB0000187 C00065 Aminoacyl-tRNA biosynthesis;Cyanoamino acid metabolism;Cysteine and methionine metabolism;Glycine, serine and threonine metabolism;Methane metabolism;Sphingolipid metabolism;Sulfur metabolism Sorbitol HMDB0000247 C00794 Fructose and mannose metabolism;Galactose metabolism Succinimide HMDB0240653 C07273 NA Threonic acid HMDB0000943 C01620 Ascorbate and aldarate metabolism Tyrosine HMDB0000158 C00082 Aminoacyl-tRNA biosynthesis;Nitrogen metabolism;Phenylalanine metabolism;Phenylalanine, tyrosine and tryptophan biosynthesis;Thiamine metabolism;Tyrosine metabolism;Ubiquinone and other terpenoid-quinone biosynthesis Uracil HMDB0000300 C00106 beta-Alanine metabolism;Pantothenate and CoA biosynthesis;Pyrimidine metabolism Valine HMDB0000883 C00183 Aminoacyl-tRNA biosynthesis;Pantothenate and CoA biosynthesis;Propanoate metabolism;Valine, leucine and isoleucine biosynthesis;Valine, leucine and isoleucine degradation Vanillin HMDB0012308 C00755 NA METABOLITES_END #END