#METABOLOMICS WORKBENCH Shiyang_Song200411_20210910_133624 DATATRACK_ID:2834 STUDY_ID:ST001916 ANALYSIS_ID:AN003114 PROJECT_ID:000000 VERSION 1 CREATED_ON September 13, 2021, 5:28 pm #PROJECT PR:PROJECT_TITLE Myocardial Rev-erb-mediated diurnal metabolic rhythm PR:PROJECT_SUMMARY Agonists and antagonists of nuclear receptor Rev-erbα/β, key components of the PR:PROJECT_SUMMARY circadian clock, can benefit the heart. Here, we show that mice with PR:PROJECT_SUMMARY cardiomyocyte-specific knockout (KO) of Rev-erbα/β display progressive cardiac PR:PROJECT_SUMMARY dilation and lethal heart failure. Inducible ablation of Rev-erbα/β in adult PR:PROJECT_SUMMARY hearts causes similar phenotypes. Impaired fatty acid oxidation in the KO PR:PROJECT_SUMMARY myocardium, particularly in the light cycle, precedes contractile dysfunctions PR:PROJECT_SUMMARY with a reciprocal overreliance on carbohydrate utilization, particularly in the PR:PROJECT_SUMMARY dark cycle. These findings delineate temporal coordination between PR:PROJECT_SUMMARY clock-mediated anticipation and nutrient-induced response in myocardial PR:PROJECT_SUMMARY metabolism. PR:INSTITUTE Baylor College of Medicine PR:LAST_NAME Song PR:FIRST_NAME Shiyang PR:ADDRESS One Baylor Plaza PR:EMAIL shiyangs@bcm.edu PR:PHONE 7137983159 #STUDY ST:STUDY_TITLE Myocardial Rev-erb-mediated diurnal metabolic rhythm (Part 2/3) ST:STUDY_SUMMARY Agonists and antagonists of nuclear receptor Rev-erbα/β, key components of the ST:STUDY_SUMMARY circadian clock, can benefit the heart. Here, we show that mice with ST:STUDY_SUMMARY cardiomyocyte-specific knockout (KO) of Rev-erbα/β display progressive cardiac ST:STUDY_SUMMARY dilation and lethal heart failure. Inducible ablation of Rev-erbα/β in adult ST:STUDY_SUMMARY hearts causes similar phenotypes. Impaired fatty acid oxidation in the KO ST:STUDY_SUMMARY myocardium, particularly in the light cycle, precedes contractile dysfunctions ST:STUDY_SUMMARY with a reciprocal overreliance on carbohydrate utilization, particularly in the ST:STUDY_SUMMARY dark cycle. These findings delineate temporal coordination between ST:STUDY_SUMMARY clock-mediated anticipation and nutrient-induced response in myocardial ST:STUDY_SUMMARY metabolism. ST:INSTITUTE Baylor College of Medicine ST:LAST_NAME Song ST:FIRST_NAME Shiyang ST:ADDRESS One Baylor Plaza,Houston, TX, 77030 ST:EMAIL shiyangs@bcm.edu ST:PHONE 7137983159 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Raw file names and additional sample data SUBJECT_SAMPLE_FACTORS - WT_CD_1 Group:WT_CD | Genotype:wild type control | Experimental variables:heart ventrcle harvest from WT mouse fed with chow diet age(months)=4.5; species=mouse; strain=C57bl/6; tissue=heart; RAW_FILE_NAME=RevCKOdiet.zip SUBJECT_SAMPLE_FACTORS - WT_CD_2 Group:WT_CD | Genotype:wild type control | Experimental variables:heart ventrcle harvest from WT mouse fed with chow diet age(months)=4.5; species=mouse; strain=C57bl/6; tissue=heart; RAW_FILE_NAME=RevCKOdiet.zip SUBJECT_SAMPLE_FACTORS - WT_CD_3 Group:WT_CD | Genotype:wild type control | Experimental variables:heart ventrcle harvest from WT mouse fed with chow diet age(months)=4.5; species=mouse; strain=C57bl/6; tissue=heart; RAW_FILE_NAME=RevCKOdiet.zip SUBJECT_SAMPLE_FACTORS - KO_CD_1 Group:KO_CD | Genotype:Rev-erb cardiomyocyte specific knock out | Experimental variables:heart ventrcle harvest from KO mouse fed with chow diet age(months)=4.5; species=mouse; strain=C57bl/6; tissue=heart; RAW_FILE_NAME=RevCKOdiet.zip SUBJECT_SAMPLE_FACTORS - KO_CD_2 Group:KO_CD | Genotype:Rev-erb cardiomyocyte specific knock out | Experimental variables:heart ventrcle harvest from KO mouse fed with chow diet age(months)=4.5; species=mouse; strain=C57bl/6; tissue=heart; RAW_FILE_NAME=RevCKOdiet.zip SUBJECT_SAMPLE_FACTORS - KO_CD_3 Group:KO_CD | Genotype:Rev-erb cardiomyocyte specific knock out | Experimental variables:heart ventrcle harvest from KO mouse fed with chow diet age(months)=4.5; species=mouse; strain=C57bl/6; tissue=heart; RAW_FILE_NAME=RevCKOdiet.zip SUBJECT_SAMPLE_FACTORS - WT_HFHSD_1 Group:WT_HFHSD | Genotype:wild type control | Experimental variables:heart ventrcle harvest from WT mouse fed with high fat high sucrose diet age(months)=4.5; species=mouse; strain=C57bl/6; tissue=heart; RAW_FILE_NAME=RevCKOdiet.zip SUBJECT_SAMPLE_FACTORS - WT_HFHSD_2 Group:WT_HFHSD | Genotype:wild type control | Experimental variables:heart ventrcle harvest from WT mouse fed with high fat high sucrose diet age(months)=4.5; species=mouse; strain=C57bl/6; tissue=heart; RAW_FILE_NAME=RevCKOdiet.zip SUBJECT_SAMPLE_FACTORS - WT_HFHSD_3 Group:WT_HFHSD | Genotype:wild type control | Experimental variables:heart ventrcle harvest from WT mouse fed with high fat high sucrose diet age(months)=4.5; species=mouse; strain=C57bl/6; tissue=heart; RAW_FILE_NAME=RevCKOdiet.zip SUBJECT_SAMPLE_FACTORS - KO-HFHSD_1 Group:KO-HFHSD | Genotype:Rev-erb cardiomyocyte specific knock out | Experimental variables:heart ventrcle harvest from KOmouse fed with high fat high sucrose diet age(months)=4.5; species=mouse; strain=C57bl/6; tissue=heart; RAW_FILE_NAME=RevCKOdiet.zip SUBJECT_SAMPLE_FACTORS - KO-HFHSD_2 Group:KO-HFHSD | Genotype:Rev-erb cardiomyocyte specific knock out | Experimental variables:heart ventrcle harvest from KOmouse fed with high fat high sucrose diet age(months)=4.5; species=mouse; strain=C57bl/6; tissue=heart; RAW_FILE_NAME=RevCKOdiet.zip SUBJECT_SAMPLE_FACTORS - KO-HFHSD_3 Group:KO-HFHSD | Genotype:Rev-erb cardiomyocyte specific knock out | Experimental variables:heart ventrcle harvest from KOmouse fed with high fat high sucrose diet age(months)=4.5; species=mouse; strain=C57bl/6; tissue=heart; RAW_FILE_NAME=RevCKOdiet.zip #COLLECTION CO:COLLECTION_SUMMARY Snap-frozen heart ventricles were collected from both WT and Rev-erb CO:COLLECTION_SUMMARY cardiomyocyte-specific KO mice fed with either chow diet or high fat high CO:COLLECTION_SUMMARY sucrose diet(HFHSD), HFHSD start at 8 weeks old and mice were harvest at 4.5 CO:COLLECTION_SUMMARY months of age. CO:SAMPLE_TYPE Heart #TREATMENT TR:TREATMENT_SUMMARY mice were fed with either the chow diet or high-fat high sucrose diet as TR:TREATMENT_SUMMARY indicated. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Heart ventricle tissues were harvested from male mice at 2.5 months of age (n = SP:SAMPLEPREP_SUMMARY 3 at each condition) and snap-frozen in liquid nitrogen. Data were acquired in SP:SAMPLEPREP_SUMMARY multiple reaction monitoring (MRM) using Agilent QQQ LC-MS systems. Separation SP:SAMPLEPREP_SUMMARY of TCA and glycolysis metabolites were performed using 5 mM ammonium acetate in SP:SAMPLEPREP_SUMMARY water as buffer pH 9.9 (A), and 100% acetonitrile as buffer (B) using Luna 3 µM SP:SAMPLEPREP_SUMMARY NH2 column (Phenomenex, Torrance, CA) and measured 6495 triple quadrupole mass SP:SAMPLEPREP_SUMMARY spectrometer via ESI negative mode (Agilent Technologies, Santa Clara, CA). The SP:SAMPLEPREP_SUMMARY Gradient used is as follows: 0-20 min-80% B (Flow rate 0.2ml/min); 20-20.10 min- SP:SAMPLEPREP_SUMMARY 80% to 2 % B; 20.10-25 min-2% B (Flow rate 0.3ml/min); 25-30 min 80% B (Flowrate SP:SAMPLEPREP_SUMMARY 0.35ml/min); 30-35 min-80%B (Flow rate 0.4ml/min); 35-38 min 80% B (Flow rate SP:SAMPLEPREP_SUMMARY 0.4ml/min); followed by re-equilibration at the end of the gradient to the SP:SAMPLEPREP_SUMMARY initial starting condition 80% B at Flow rate of 0.2 ml/min. Separation and SP:SAMPLEPREP_SUMMARY measurement of amino acids were performed using Zorbax eclipse XDB C-18, 1.8 SP:SAMPLEPREP_SUMMARY micron, 4.6 x 100 mm column on 6495 triple quadrupole mass spectrometer via ESI SP:SAMPLEPREP_SUMMARY Positive mode (Agilent Technologies, Santa Clara, CA). Mobile phases A and B SP:SAMPLEPREP_SUMMARY were 0.1% formic acid in water and acetonitrile, respectively. The gradient used SP:SAMPLEPREP_SUMMARY is as follows: 0 min-2% B; 6 min- 2% of B, 6.5 min-30 % B, 7 min- 90% of B, 12 SP:SAMPLEPREP_SUMMARY min 95% of B, 13 min 2% of B followed by re-equilibration at the end of the SP:SAMPLEPREP_SUMMARY gradient 20 min to the initial starting condition 2% of B. Flow rate: 0.2 SP:SAMPLEPREP_SUMMARY ml/min. Separation and measurement of CoA's and carnitines were performed using SP:SAMPLEPREP_SUMMARY Zorbax eclipse XDB C-18, 1.8 micron, 4.6 x 100 mm column on 6495 triple SP:SAMPLEPREP_SUMMARY quadrupole mass spectrometer via ESI Positive mode (Agilent Technologies, Santa SP:SAMPLEPREP_SUMMARY Clara, CA). Mobile phases A and B were 0.1% formic acid in water and SP:SAMPLEPREP_SUMMARY acetonitrile, respectively. Gradient used is as follows: 0 min-2% B; 6 min- 2% SP:SAMPLEPREP_SUMMARY of B, 6.5 min-30 % B, 7 min- 90% of B, 12 min 95% of B,13 min 2% of B followed SP:SAMPLEPREP_SUMMARY by re-equilibration at end of the gradient 20 min to the initial starting SP:SAMPLEPREP_SUMMARY condition 2% of B. Flow rate: 0.2 ml/min. Separation and measurement of SP:SAMPLEPREP_SUMMARY nucleotides were performed using Zorbax eclipse XDB C-18, 1.8 micron, 4.6 x 100 SP:SAMPLEPREP_SUMMARY mm column on 6495 triple quadrupole mass spectrometer via ESI Positive mode SP:SAMPLEPREP_SUMMARY (Agilent Technologies, Santa Clara, CA). Mobile phases A and B were 0.1% formic SP:SAMPLEPREP_SUMMARY acid in water and acetonitrile, respectively. The gradient used is as follows: SP:SAMPLEPREP_SUMMARY 0-6 min 2% B, 6-6.50 min 30% B, 7-12 min 95% B, 12-13 min 2% B, and SP:SAMPLEPREP_SUMMARY re-equilibration till the end of the gradient 20 min. Flow rate: 0.2 ml/min). SP:SAMPLEPREP_SUMMARY The data were normalized with internal standards, and log2 transformed on a SP:SAMPLEPREP_SUMMARY per-sample, per-method basis. Statistical analyses were performed with either SP:SAMPLEPREP_SUMMARY ANOVA or t-test in R Studio (R Studio Inc., Boston, MA). Differential SP:SAMPLEPREP_SUMMARY metabolites were identified by adjusting the p-values for multiple testing at an SP:SAMPLEPREP_SUMMARY FDR (Benjamini Hochberg method) threshold of <0.25. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY Heart ventricle tissues were harvested from male mice at 2.5 months of age (n = CH:CHROMATOGRAPHY_SUMMARY 3 at each condition) and snap-frozen in liquid nitrogen. Data were acquired in CH:CHROMATOGRAPHY_SUMMARY multiple reaction monitoring (MRM) using Agilent QQQ LC-MS systems. Separation CH:CHROMATOGRAPHY_SUMMARY of TCA and glycolysis metabolites were performed using 5 mM ammonium acetate in CH:CHROMATOGRAPHY_SUMMARY water as buffer pH 9.9 (A), and 100% acetonitrile as buffer (B) using Luna 3 µM CH:CHROMATOGRAPHY_SUMMARY NH2 column (Phenomenex, Torrance, CA) and measured 6495 triple quadrupole mass CH:CHROMATOGRAPHY_SUMMARY spectrometer via ESI negative mode (Agilent Technologies, Santa Clara, CA). The CH:CHROMATOGRAPHY_SUMMARY Gradient used is as follows: 0-20 min-80% B (Flow rate 0.2ml/min); 20-20.10 min- CH:CHROMATOGRAPHY_SUMMARY 80% to 2 % B; 20.10-25 min-2% B (Flow rate 0.3ml/min); 25-30 min 80% B (Flowrate CH:CHROMATOGRAPHY_SUMMARY 0.35ml/min); 30-35 min-80%B (Flow rate 0.4ml/min); 35-38 min 80% B (Flow rate CH:CHROMATOGRAPHY_SUMMARY 0.4ml/min); followed by re-equilibration at the end of the gradient to the CH:CHROMATOGRAPHY_SUMMARY initial starting condition 80% B at Flow rate of 0.2 ml/min. Separation and CH:CHROMATOGRAPHY_SUMMARY measurement of amino acids were performed using Zorbax eclipse XDB C-18, 1.8 CH:CHROMATOGRAPHY_SUMMARY micron, 4.6 x 100 mm column on 6495 triple quadrupole mass spectrometer via ESI CH:CHROMATOGRAPHY_SUMMARY Positive mode (Agilent Technologies, Santa Clara, CA). Mobile phases A and B CH:CHROMATOGRAPHY_SUMMARY were 0.1% formic acid in water and acetonitrile, respectively. The gradient used CH:CHROMATOGRAPHY_SUMMARY is as follows: 0 min-2% B; 6 min- 2% of B, 6.5 min-30 % B, 7 min- 90% of B, 12 CH:CHROMATOGRAPHY_SUMMARY min 95% of B, 13 min 2% of B followed by re-equilibration at the end of the CH:CHROMATOGRAPHY_SUMMARY gradient 20 min to the initial starting condition 2% of B. Flow rate: 0.2 CH:CHROMATOGRAPHY_SUMMARY ml/min. Separation and measurement of CoA's and carnitines were performed using CH:CHROMATOGRAPHY_SUMMARY Zorbax eclipse XDB C-18, 1.8 micron, 4.6 x 100 mm column on 6495 triple CH:CHROMATOGRAPHY_SUMMARY quadrupole mass spectrometer via ESI Positive mode (Agilent Technologies, Santa CH:CHROMATOGRAPHY_SUMMARY Clara, CA). Mobile phases A and B were 0.1% formic acid in water and CH:CHROMATOGRAPHY_SUMMARY acetonitrile, respectively. Gradient used is as follows: 0 min-2% B; 6 min- 2% CH:CHROMATOGRAPHY_SUMMARY of B, 6.5 min-30 % B, 7 min- 90% of B, 12 min 95% of B,13 min 2% of B followed CH:CHROMATOGRAPHY_SUMMARY by re-equilibration at end of the gradient 20 min to the initial starting CH:CHROMATOGRAPHY_SUMMARY condition 2% of B. Flow rate: 0.2 ml/min. Separation and measurement of CH:CHROMATOGRAPHY_SUMMARY nucleotides were performed using Zorbax eclipse XDB C-18, 1.8 micron, 4.6 x 100 CH:CHROMATOGRAPHY_SUMMARY mm column on 6495 triple quadrupole mass spectrometer via ESI Positive mode CH:CHROMATOGRAPHY_SUMMARY (Agilent Technologies, Santa Clara, CA). Mobile phases A and B were 0.1% formic CH:CHROMATOGRAPHY_SUMMARY acid in water and acetonitrile, respectively. The gradient used is as follows: CH:CHROMATOGRAPHY_SUMMARY 0-6 min 2% B, 6-6.50 min 30% B, 7-12 min 95% B, 12-13 min 2% B, and CH:CHROMATOGRAPHY_SUMMARY re-equilibration till the end of the gradient 20 min. Flow rate: 0.2 ml/min). CH:CHROMATOGRAPHY_SUMMARY The data were normalized with internal standards, and log2 transformed on a CH:CHROMATOGRAPHY_SUMMARY per-sample, per-method basis. Statistical analyses were performed with either CH:CHROMATOGRAPHY_SUMMARY ANOVA or t-test in R Studio (R Studio Inc., Boston, MA). Differential CH:CHROMATOGRAPHY_SUMMARY metabolites were identified by adjusting the p-values for multiple testing at an CH:CHROMATOGRAPHY_SUMMARY FDR (Benjamini Hochberg method) threshold of <0.25. CH:CHROMATOGRAPHY_TYPE GC CH:INSTRUMENT_NAME Agilent 1290 CH:COLUMN_NAME Agilent Zorbax Eclipse Plus C18 (100 x 2.1mm, 1.8 um) #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Agilent 6490 QQQ MS:INSTRUMENT_TYPE Other MS:MS_TYPE ESI MS:ION_MODE POSITIVE MS:MS_COMMENTS The data were normalized with internal standards, and log2 transformed on a MS:MS_COMMENTS per-sample, per-method basis. Statistical analyses were performed with either MS:MS_COMMENTS ANOVA or t-test in R Studio (R Studio Inc., Boston, MA). Differential MS:MS_COMMENTS metabolites were identified by adjusting the p-values for multiple testing at an MS:MS_COMMENTS FDR (Benjamini Hochberg method) threshold of <0.25. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS pmoles/l MS_METABOLITE_DATA_START Samples WT_CD_1 WT_CD_2 WT_CD_3 KO_CD_1 KO_CD_2 KO_CD_3 WT_HFHSD_1 WT_HFHSD_2 WT_HFHSD_3 KO-HFHSD_1 KO-HFHSD_2 KO-HFHSD_3 Factors Group:WT_CD | Genotype:wild type control | Experimental variables:heart ventrcle harvest from WT mouse fed with chow diet Group:WT_CD | Genotype:wild type control | Experimental variables:heart ventrcle harvest from WT mouse fed with chow diet Group:WT_CD | Genotype:wild type control | Experimental variables:heart ventrcle harvest from WT mouse fed with chow diet Group:KO_CD | Genotype:Rev-erb cardiomyocyte specific knock out | Experimental variables:heart ventrcle harvest from KO mouse fed with chow diet Group:KO_CD | Genotype:Rev-erb cardiomyocyte specific knock out | Experimental variables:heart ventrcle harvest from KO mouse fed with chow diet Group:KO_CD | Genotype:Rev-erb cardiomyocyte specific knock out | Experimental variables:heart ventrcle harvest from KO mouse fed with chow diet Group:WT_HFHSD | Genotype:wild type control | Experimental variables:heart ventrcle harvest from WT mouse fed with high fat high sucrose diet Group:WT_HFHSD | Genotype:wild type control | Experimental variables:heart ventrcle harvest from WT mouse fed with high fat high sucrose diet Group:WT_HFHSD | Genotype:wild type control | Experimental variables:heart ventrcle harvest from WT mouse fed with high fat high sucrose diet Group:KO-HFHSD | Genotype:Rev-erb cardiomyocyte specific knock out | Experimental variables:heart ventrcle harvest from KOmouse fed with high fat high sucrose diet Group:KO-HFHSD | Genotype:Rev-erb cardiomyocyte specific knock out | Experimental variables:heart ventrcle harvest from KOmouse fed with high fat high sucrose diet Group:KO-HFHSD | Genotype:Rev-erb cardiomyocyte specific knock out | Experimental variables:heart ventrcle harvest from KOmouse fed with high fat high sucrose diet Alanine -2.220278098 -1.64067611 -1.284423874 -1.701284354 -1.987770791 -1.686866086 -2.177782496 -1.932152075 -1.661779595 -1.695203748 -1.802323601 -2.297759189 Arginine -1.92296464 -1.555360589 -1.434931304 -2.557416109 -2.128414108 -1.791413965 -1.400997564 -1.472726624 -1.013927481 -1.216499826 -1.432509191 -1.28412705 Asparagine -0.159295876 -0.65904227 -0.503348945 -0.328640024 -0.45440137 0.075477381 0.22649214 -0.575614905 -0.174352573 -0.045002976 -0.935162288 -1.372765701 Aspartic acid -3.7233828 -4.086707945 -4.024967702 -3.110121437 -3.016956848 -2.43531228 -4.704395227 -4.557583164 -4.482096695 -3.495198668 -3.631666293 -3.798707691 Betaine 0.206761827 -0.290343211 -1.005269562 0.207507327 0.363120175 0.164161965 -1.050198518 -1.58412704 -1.011811928 0.256616199 0.117070313 -0.130884639 Citrulline -4.463614704 -4.264140452 -3.796612194 -3.850167223 -3.765672174 -3.402661076 -2.707146545 -3.140183397 -2.872855341 -2.570382924 -2.769973901 -2.591729463 Cystine -6.838751662 -7.209769871 -6.888871463 -7.769905585 -7.22343719 -7.104681619 -6.914813848 -7.975952217 -7.184332423 -7.290334575 -7.54466992 -7.656977219 Glucosamine -6.340338736 -6.250981917 -6.385005879 -6.389096605 -6.564978313 -6.238704219 -6.26312481 -6.266873592 -6.33204374 -6.049868081 -6.624333307 -6.268866803 Glutaric acid -10.11526408 -11.16034211 -10.70253097 -11.0980966 -10.32058757 -9.878499917 -11.12053589 -10.83153058 -9.632421516 -9.464708841 -9.89839886 -9.366196254 Glycine -8.350138379 -7.654170031 -7.424005415 -7.687232929 -8.700335813 -8.092204933 -7.773183738 -8.242562502 -7.583066251 -7.141761882 -6.821952162 -7.390819071 Guanine -2.762339168 -2.868879386 -2.617980378 -2.699683071 -1.830344251 -1.391504078 -2.792210487 -3.155695881 -2.496148043 -1.435653193 -1.598254024 -1.60229636 Histidine -2.553281657 -2.617863976 -2.593186629 -2.797874815 -2.907350266 -2.200674948 -2.314705836 -2.563687489 -2.347678507 -2.259198548 -2.38756117 -2.526549704 Homocysteine -10.64295582 -9.351021248 -10.4092405 -11.68695525 -10.29024434 -11.17438231 -11.59277699 -10.75178295 -10.50129692 -11.16190824 -9.973488202 -10.17781272 Isoleucine 4.29101476 3.84141581 3.86400251 3.835096416 3.786065101 4.232115548 4.190999809 3.704002382 4.179565269 4.174235919 3.975723862 3.77525598 Lysine -0.756337433 -0.106921752 -0.377860339 0.723277987 0.782145466 1.418807792 1.684567517 1.19263953 1.738114942 1.432350723 1.15610139 1.241816142 Methionine -0.928269346 -0.789351324 -0.906400057 -0.655948995 -0.691954293 -0.250738595 -0.763159917 -1.409707363 -1.089905568 -0.588943297 -0.862189266 -0.546046011 N-acetyl AA -9.417644869 -9.168308876 -9.243993677 -8.013225559 -7.674315554 -7.908586917 -9.338061205 -9.774128438 -9.257610509 -7.557440012 -7.677837267 -8.138795483 Ornithine -3.612781405 -4.265281286 -4.157677631 -3.865540315 -3.941018312 -3.490046828 -3.732407376 -4.265214717 -3.687615259 -3.571618229 -3.441399278 -3.931518211 Phenyl alanine 2.970740079 2.354495311 2.524758545 2.734537111 2.577645168 3.295402763 2.693178181 2.264257053 2.558235321 2.959938115 2.941764666 2.777092365 Proline -2.296367276 -2.242562667 -2.609444592 -0.954149506 -0.542084202 -0.458672674 -1.441028379 -1.464221195 -1.613539575 -0.051865625 -0.46261918 -0.529288572 Putrescine -6.312349009 -6.645407906 -6.932221347 -5.232523275 -5.050703103 -5.238374636 -7.259045771 -7.65155597 -7.233199557 -5.74069515 -6.095853698 -5.787043302 Serine -6.177896656 -6.23217853 -6.629379365 -4.444357413 -4.735186503 -4.132324867 -4.381695393 -4.489257521 -4.786365504 -3.661569496 -4.178906934 -4.078921058 Spermidine -4.004627782 -4.073087195 -3.86376483 -1.414081342 -1.813601817 -1.952493385 -4.548625456 -4.229446633 -3.617518743 -2.227636816 -3.140793939 -2.402464285 Spermine -7.903765273 -8.174950747 -8.873281844 -8.296856702 -8.551487588 -9.401342617 -9.946016989 -10.6588205 -8.536950595 -8.692337132 -9.741695951 -9.429546589 Threonine -3.878357362 -3.752536217 -3.574300138 -3.51092912 -3.610496792 -2.679078806 -3.003020874 -2.981315395 -3.191484373 -2.625734248 -2.506268404 -2.561274961 Tryptophan 1.371571515 2.021194505 1.747721251 1.60497682 1.740804917 2.229190051 1.779117034 1.716897922 2.113404916 2.013494727 2.03902674 1.869642631 Tyrosine 0.142722301 0.547947607 0.703438067 0.501651296 0.647641035 1.472942703 0.652449056 0.189306107 0.526959981 0.899839996 0.977386455 1.019149636 Valine 1.149377381 0.440050922 0.292049599 0.642065835 0.567125792 0.806836768 0.980107926 0.267155477 0.792949087 0.994928445 0.744778156 0.484488424 2-Methylbutyrylcarnitine -3.120820083 -3.50990973 -3.160621569 -4.000838484 -4.578263498 -3.709286484 -3.896109318 -3.789594884 -3.795862715 -4.075701314 -3.90252409 -4.155344816 Acetyl Carnitine 2.310929307 2.169851644 2.35746096 2.483699203 2.920937899 2.489112472 3.323724465 3.569360646 3.616060255 2.335482231 2.287614763 2.860999102 Butyrylcarnitine 0.958913724 0.629910252 0.989736381 -1.139333805 -1.689481817 -0.923434901 1.386449745 1.736076167 1.436126481 -1.273562745 -2.060031848 -0.801169489 Deoxy carnitine -2.905329381 -2.661051746 -2.767143742 -1.666816092 -2.055826698 -1.47951379 -3.149100409 -2.697732527 -2.90349242 -2.598486097 -2.956353504 -2.538379705 GlutaroylCoA -15.59399136 -15.39308189 -16.71706394 -14.4225628 -15.18124201 -13.94443108 -13.86207022 -14.59583129 -14.03439672 -14.97845661 -14.08686435 -15.35205594 Carnitine 0.624407662 1.348769492 1.63041673 0.567132398 0.615740612 0.864400261 0.843807905 0.78262694 0.981717343 0.278990324 0.333068641 0.344450623 Heptanoyl Carnitine -0.1241847 -0.338497542 -0.224087244 -3.483658414 -3.4521152 -3.628024894 -0.198987811 0.507648516 0.758278026 -2.566268272 -3.310878065 -2.941047072 Isobutyryl Carnitine 0.758482978 0.629406806 0.774871647 -2.343914573 -2.061816466 -1.570052561 1.417309736 1.21734433 0.889920965 -1.74352727 -2.299859822 -1.206285739 Isovaleryl Carnitine -0.278821403 -0.861076036 -0.514703494 -1.461276806 -1.948717618 -1.19881481 -1.139548521 -0.693994879 -1.12384254 -1.936399881 -1.538500785 -1.865377157 Malonylcarnitine -5.086890368 -4.946050714 -5.696873885 -6.929977683 -7.731621726 -7.089693986 -5.134459407 -5.188119887 -5.225660998 -6.550017719 -6.59711161 -6.058748226 Octanoylcarnitine 1.186483271 0.829973679 0.545800702 -3.18640156 -3.031075721 -2.678836642 1.289234939 1.711301303 1.519579515 -2.328754564 -2.696615103 -2.876920651 MethylGlutaryl carnitine -7.736323935 -7.558983958 -7.89367239 -9.387850694 -9.617545525 -9.730237765 -7.466050508 -7.796165768 -7.075942501 -8.831977107 -8.490788601 -8.687226821 Palmitoylcarnitine -4.229023174 -5.170229978 -5.848227644 -7.980982354 -8.018669073 -7.162696251 -3.428311036 -4.022632584 -4.867107089 -8.829348524 -8.131596991 -8.939132027 Palmityl Carnitine -2.34307506 -5.54933381 -6.248300009 -8.312052688 -7.994451856 -7.935864938 -3.391008474 -4.04706552 -5.002598777 -8.509898678 -7.949166359 -8.891321165 Propionyl Carnitine 0.769138187 0.987513003 0.86244826 -0.825532172 -0.664846323 -0.486257637 0.303613079 1.13997941 0.962563229 -1.038736624 -0.772479821 -1.074555965 Succinyl CoA -12.6224133 -14.18416051 -14.09465811 -13.07625154 -13.5299124 -13.91681356 -14.88404285 -15.40277804 -14.18855583 -13.22229137 -13.7699144 -13.14681441 3PG and 2PG -2.583455233 -2.672492164 -2.520603736 -2.663501847 -2.55889444 -3.320299072 -3.35783835 -2.950907391 -2.940626586 -3.702383522 -3.755118027 -3.990900763 Citrate 6.335308728 6.284536879 5.967287258 5.473943864 6.452470409 5.638595169 6.47536093 7.368072315 7.021597124 6.736479622 6.485090897 6.696874677 Erythrose-4-P -3.34963405 -2.885206077 -2.66129703 -1.906160741 -1.933847079 -1.850086886 -3.182958008 -2.668824383 -3.286258345 -2.619238874 -2.196569822 -2.429276848 FBP/GBP -3.153081153 -2.755746269 -2.386886574 2.427224475 2.333546303 2.1667404 -0.806521876 -0.316741578 -0.934711699 1.150000869 0.567867873 1.131667699 Fumarate 1.420182807 1.668934283 1.8729203 1.230558983 1.356528956 0.939158297 1.501630443 1.369769947 1.046082849 1.529768334 1.589845459 1.475907005 G6P/F6P 1.451045348 0.9621117 1.598520538 4.053432553 4.242638838 3.847154982 1.676393915 1.899492 1.84414692 3.467336828 3.551447582 3.926187354 GlucoseFructose 1.964776682 1.895230094 2.003556897 3.017691083 2.882384319 2.993434502 2.355585662 2.838750656 2.21173323 2.666377791 2.686595368 2.868144282 Glutamic acid 5.572320572 5.430830138 5.158813535 5.473917169 5.584642093 5.589736158 6.011899099 6.100141729 6.274676785 5.667285609 5.557717567 5.78069152 Glutamine 1.93665789 2.060444334 2.481236933 2.402830031 2.248757158 1.970221521 2.71793794 2.529470069 2.784652683 2.25925317 2.223907506 2.372954159 Glycerol 3 Phosphate -1.192245241 -1.294413103 -0.559160559 -2.476863739 -2.476240826 -2.322728175 -0.325696388 -0.223973657 -0.223404196 -2.247051035 -2.017120419 -1.681453246 Hydroxy glutarate 0.538439488 0.976456702 0.667056287 1.034867717 1.227838561 1.205266959 1.651335624 1.648284495 1.895403827 1.225044487 1.043005984 1.442153479 Ketoglutarate -0.542264609 -0.82576794 -0.564197673 -0.919820293 -0.814751327 -0.960798013 -1.656590918 -0.785143362 -0.61593739 -0.817129388 -0.914289674 -0.711879522 Lactate 3.900923992 3.817861354 3.987633775 4.456324206 4.497308342 4.617274691 4.131099749 4.541795571 4.078594198 4.330832216 4.443247962 4.343049351 Malate 6.069124502 5.826376937 5.827576185 5.73978434 6.168967001 6.285692597 6.149621925 5.80781698 5.64751009 6.044362237 6.124661868 6.233660281 OAA -3.380374837 -3.319616771 -3.346982204 -2.729850658 -2.973922599 -3.091170432 -3.671382098 -3.650307964 -2.871325745 -2.709297672 -2.468805947 -1.877482499 Ribose/Ribulose/xylulose-5P 2.368248715 2.841015606 2.761882609 3.037453177 2.902563029 2.85079028 2.438717691 2.469434221 2.609093847 2.897330493 2.696071049 3.029735867 Sedoheptulose-7-P -3.313500175 -3.581461269 -3.383542019 -2.927997452 -3.05674521 -2.909372522 -3.234350057 -3.564685573 -3.274661643 -3.090305091 -3.37298826 -3.139671478 Succinate -0.315149075 -0.406499056 -0.644952251 -1.591157506 -1.678454263 -1.616328051 0.897444673 1.113003721 0.854945397 -1.252944324 -1.478373737 -0.765408759 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Alanine Arginine Asparagine Aspartic acid Betaine Citrulline Cystine Glucosamine Glutaric acid Glycine Guanine Histidine Homocysteine Isoleucine Lysine Methionine N-acetyl AA Ornithine Phenyl alanine Proline Putrescine Serine Spermidine Spermine Threonine Tryptophan Tyrosine Valine 2-Methylbutyrylcarnitine Acetyl Carnitine Butyrylcarnitine Deoxy carnitine GlutaroylCoA Carnitine Heptanoyl Carnitine Isobutyryl Carnitine Isovaleryl Carnitine Malonylcarnitine Octanoylcarnitine MethylGlutaryl carnitine Palmitoylcarnitine Palmityl Carnitine Propionyl Carnitine Succinyl CoA 3PG and 2PG Citrate Erythrose-4-P FBP/GBP Fumarate G6P/F6P GlucoseFructose Glutamic acid Glutamine Glycerol 3 Phosphate Hydroxy glutarate Ketoglutarate Lactate Malate OAA Ribose/Ribulose/xylulose-5P Sedoheptulose-7-P Succinate METABOLITES_END #END