#METABOLOMICS WORKBENCH hormel101_20160923_070303_mwtab.txt DATATRACK_ID:747 VERSION 1 CREATED_ON November 17, 2016, 3:09 pm #PROJECT PR:PROJECT_TITLE Mechanism by Which Caloric Restriction Improves Insulin Sensitivity in Sedentary PR:PROJECT_TITLE Obese Adults PR:PROJECT_TYPE skeletal muscle ceramide, diacylglycerol, or amino acid metabolite levels PR:PROJECT_SUMMARY effect of caloric restriction on insulin sensitivity through skeletal muscle PR:PROJECT_SUMMARY ceramide, diacylglycerol, or amino acid metabolite levels PR:INSTITUTE Mayo Clinic PR:DEPARTMENT Endocrinology PR:LABORATORY Mayo Clinic Metabolomics Resource Core PR:LAST_NAME Nair PR:FIRST_NAME Sreekumaran PR:ADDRESS 200 First Street SW, Rochester, MN 55905 PR:EMAIL Nair.K@mayo.edu PR:PHONE 507-285-2415 #STUDY ST:STUDY_TITLE Amino Acid Quantifcation of obese patients on a 16 week caloric restriction from ST:STUDY_TITLE muscle biopsy (part II) ST:STUDY_TYPE timecourse, quantitative measurements of amino acid ST:STUDY_SUMMARY Caloric restriction (CR) improves insulin sensitivity and reduces the incidence ST:STUDY_SUMMARY of diabetes in obese individuals. The underlying mechanisms whereby CR improves ST:STUDY_SUMMARY insulin sensitivity are not clear. We evaluated the effect of 16 weeks of CR on ST:STUDY_SUMMARY whole-body insulin sensitivity by pancreatic clamp before and after CR in 11 ST:STUDY_SUMMARY obese participants (BMI = 35 kg/m2) compared with 9 matched control subjects ST:STUDY_SUMMARY (BMI = 34 kg/m2). Compared with the control subjects, CR increased the glucose ST:STUDY_SUMMARY infusion rate needed to maintain euglycemia during hyperinsulinemia, indicating ST:STUDY_SUMMARY enhancement of peripheral insulin sensitivity. This improvement in insulin ST:STUDY_SUMMARY sensitivity was not accompanied by changes in skeletal muscle mitochondrial ST:STUDY_SUMMARY oxidative capacity or oxidant emissions, nor were there changes in skeletal ST:STUDY_SUMMARY muscle ceramide, diacylglycerol, or amino acid metabolite levels. However, CR ST:STUDY_SUMMARY lowered insulin-stimulated thioredoxin-interacting protein (TXNIP) levels and ST:STUDY_SUMMARY enhanced nonoxidative glucose disposal. These results support a role for TXNIP ST:STUDY_SUMMARY in mediating the improvement in peripheral insulin sensitivity after CR. ST:INSTITUTE Mayo Clinic ST:DEPARTMENT Endocrinology ST:LABORATORY Mayo Clinic Metabolomics Resource Core ST:LAST_NAME Nair ST:FIRST_NAME Sreekumaran ST:ADDRESS 200 First Street SW, Rochester, MN 55905 ST:EMAIL Nair.K@mayo.edu ST:PHONE 507-285-2415 #SUBJECT SU:SUBJECT_TYPE Animal SU:SUBJECT_SPECIES Homo sapiens SU:TAXONOMY_ID 9606 #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data SUBJECT_SAMPLE_FACTORS s1 ms5370-1 Time (mins) (mins):1 | Category:Caloric Restriction mg tissue=16; sample type=muscle; Sex=F SUBJECT_SAMPLE_FACTORS s1 ms5370-2 Time (mins) (mins):2 | Category:Caloric Restriction mg tissue=15.9; sample type=muscle; Sex=F SUBJECT_SAMPLE_FACTORS s2 ms5370-3 Time (mins) (mins):1 | Category:Caloric Restriction mg tissue=24.1; sample type=muscle; Sex=F SUBJECT_SAMPLE_FACTORS s2 ms5370-4 Time (mins) (mins):2 | Category:Caloric Restriction mg tissue=16; sample type=muscle; Sex=F SUBJECT_SAMPLE_FACTORS s3 ms5370-5 Time (mins) (mins):1 | Category:Caloric Restriction mg tissue=17.6; sample type=muscle; Sex=M SUBJECT_SAMPLE_FACTORS s3 ms5370-6 Time (mins) (mins):2 | Category:Caloric Restriction mg tissue=10.6; sample type=muscle; Sex=M SUBJECT_SAMPLE_FACTORS s4 ms5370-7 Time (mins) (mins):1 | Category:Caloric Restriction mg tissue=21.8; sample type=muscle; Sex=F SUBJECT_SAMPLE_FACTORS s4 ms5370-8 Time (mins) (mins):2 | Category:Caloric Restriction mg tissue=13.4; sample type=muscle; Sex=F SUBJECT_SAMPLE_FACTORS s5 ms5370-9 Time (mins) (mins):1 | Category:Caloric Restriction mg tissue=13.1; sample type=muscle; Sex=F SUBJECT_SAMPLE_FACTORS s5 ms5370-10 Time (mins) (mins):2 | Category:Caloric Restriction mg tissue=11.8; sample type=muscle; Sex=F SUBJECT_SAMPLE_FACTORS s6 ms5370-11 Time (mins) (mins):1 | Category:Caloric Restriction mg tissue=19.7; sample type=muscle; Sex=M SUBJECT_SAMPLE_FACTORS s6 ms5370-12 Time (mins) (mins):2 | Category:Caloric Restriction mg tissue=14.5; sample type=muscle; Sex=M SUBJECT_SAMPLE_FACTORS s7 ms5370-13 Time (mins) (mins):1 | Category:Caloric Restriction mg tissue=12.6; sample type=muscle; Sex=M SUBJECT_SAMPLE_FACTORS s7 ms5370-14 Time (mins) (mins):2 | Category:Caloric Restriction mg tissue=21.3; sample type=muscle; Sex=M SUBJECT_SAMPLE_FACTORS s8 ms5370-15 Time (mins) (mins):1 | Category:Control mg tissue=24.9; sample type=muscle; Sex=M SUBJECT_SAMPLE_FACTORS s8 ms5370-16 Time (mins) (mins):2 | Category:Control mg tissue=17.3; sample type=muscle; Sex=M SUBJECT_SAMPLE_FACTORS s9 ms5370-17 Time (mins) (mins):1 | Category:Control mg tissue=11.8; sample type=muscle; Sex=F SUBJECT_SAMPLE_FACTORS s9 ms5370-18 Time (mins) (mins):2 | Category:Control mg tissue=14.3; sample type=muscle; Sex=F SUBJECT_SAMPLE_FACTORS s10 ms5370-19 Time (mins) (mins):1 | Category:Caloric Restriction mg tissue=17; sample type=muscle; Sex=F SUBJECT_SAMPLE_FACTORS s10 ms5370-20 Time (mins) (mins):2 | Category:Caloric Restriction mg tissue=14; sample type=muscle; Sex=F SUBJECT_SAMPLE_FACTORS s11 ms5370-21 Time (mins) (mins):1 | Category:Control mg tissue=24.6; sample type=muscle; Sex=F SUBJECT_SAMPLE_FACTORS s11 ms5370-22 Time (mins) (mins):2 | Category:Control mg tissue=20.9; sample type=muscle; Sex=F SUBJECT_SAMPLE_FACTORS s12 ms5370-23 Time (mins) (mins):1 | Category:Caloric Restriction mg tissue=20; sample type=muscle; Sex=M SUBJECT_SAMPLE_FACTORS s12 ms5370-24 Time (mins) (mins):2 | Category:Caloric Restriction mg tissue=18.5; sample type=muscle; Sex=M SUBJECT_SAMPLE_FACTORS s13 ms5370-25 Time (mins) (mins):1 | Category:Control mg tissue=20.7; sample type=muscle; Sex=M SUBJECT_SAMPLE_FACTORS s13 ms5370-26 Time (mins) (mins):2 | Category:Control mg tissue=25.1; sample type=muscle; Sex=M SUBJECT_SAMPLE_FACTORS s14 ms5370-27 Time (mins) (mins):1 | Category:Control mg tissue=22.1; sample type=muscle; Sex=M SUBJECT_SAMPLE_FACTORS s14 ms5370-28 Time (mins) (mins):2 | Category:Control mg tissue=20.5; sample type=muscle; Sex=M SUBJECT_SAMPLE_FACTORS s15 ms5370-29 Time (mins) (mins):1 | Category:Control mg tissue=15.8; sample type=muscle; Sex=M SUBJECT_SAMPLE_FACTORS s15 ms5370-30 Time (mins) (mins):2 | Category:Control mg tissue=11.2; sample type=muscle; Sex=M SUBJECT_SAMPLE_FACTORS s16 ms5370-31 Time (mins) (mins):1 | Category:Caloric Restriction mg tissue=12.9; sample type=muscle; Sex=M SUBJECT_SAMPLE_FACTORS s16 ms5370-32 Time (mins) (mins):2 | Category:Caloric Restriction mg tissue=21.6; sample type=muscle; Sex=M SUBJECT_SAMPLE_FACTORS s17 ms5370-33 Time (mins) (mins):1 | Category:Caloric Restriction mg tissue=12.3; sample type=muscle; Sex=F SUBJECT_SAMPLE_FACTORS s17 ms5370-34 Time (mins) (mins):2 | Category:Caloric Restriction mg tissue=24.7; sample type=muscle; Sex=F SUBJECT_SAMPLE_FACTORS s18 ms5370-35 Time (mins) (mins):1 | Category:Control mg tissue=16.4; sample type=muscle; Sex=M SUBJECT_SAMPLE_FACTORS s18 ms5370-36 Time (mins) (mins):2 | Category:Control mg tissue=12.1; sample type=muscle; Sex=M SUBJECT_SAMPLE_FACTORS s19 ms5370-37 Time (mins) (mins):1 | Category:Control mg tissue=17.4; sample type=muscle; Sex=F SUBJECT_SAMPLE_FACTORS s19 ms5370-38 Time (mins) (mins):2 | Category:Control mg tissue=22.6; sample type=muscle; Sex=F SUBJECT_SAMPLE_FACTORS s20 ms5370-39 Time (mins) (mins):1 | Category:Control mg tissue=27; sample type=muscle; Sex=F SUBJECT_SAMPLE_FACTORS s20 ms5370-40 Time (mins) (mins):2 | Category:Control mg tissue=16.5; sample type=muscle; Sex=F #COLLECTION CO:COLLECTION_SUMMARY Blood samples were collected in a heated hotbox (131°F) through a retrograde CO:COLLECTION_SUMMARY intravenous catheter at baseline for glucose and hormone levels, and every 10 CO:COLLECTION_SUMMARY min during the clamp to maintain euglycemia. In addition, blood samples were CO:COLLECTION_SUMMARY collected every 20 min from 0600 to 0700, 0900 to 1000, and 1200 to 1300 to CO:COLLECTION_SUMMARY measure plasma [6,62H2]glucose. At 1330 h, a percutaneous needle muscle biopsy CO:COLLECTION_SUMMARY specimen (350–400 mg) was obtained from the vastus lateralis muscle under CO:COLLECTION_SUMMARY local anesthesia, immediately frozen in liquid nitrogen, and stored at −80°F CO:COLLECTION_SUMMARY for future analysis (27). This biopsy sample was used for analysis of TXNIP mRNA CO:COLLECTION_SUMMARY and protein content. The participant remained in the CRU through the remainder CO:COLLECTION_SUMMARY of the day and was given a weight-maintenance diet until 2200 h. At 0700 h the CO:COLLECTION_SUMMARY following morning, a second muscle biopsy specimen was obtained under local CO:COLLECTION_SUMMARY anesthesia, and ∼100 mg was used immediately for mitochondrial function CO:COLLECTION_SUMMARY measurements of isolated mitochondria and mtH2O2 emissions (28). The remainder CO:COLLECTION_SUMMARY was immediately frozen in liquid nitrogen and stored at −80°F for future CO:COLLECTION_SUMMARY analysis, including DAG, ceramide, and amino acid measurements (Fig. 1). CO:SAMPLE_TYPE Muscle #TREATMENT TR:TREATMENT_SUMMARY Before and after 16 weeks of CR or CON, two outpatient visits and one inpatient TR:TREATMENT_SUMMARY visit were scheduled. Before the outpatient visits, participants were instructed TR:TREATMENT_SUMMARY to fast overnight from 10:00 p.m. the evening before and to avoid strenuous TR:TREATMENT_SUMMARY exercise for 24 h preceding the visits. One outpatient visit consisted of an MRI TR:TREATMENT_SUMMARY to measure subcutaneous and visceral fat distribution and magnetic resonance TR:TREATMENT_SUMMARY spectroscopy to measure skeletal muscle oxidative capacity (25). The second TR:TREATMENT_SUMMARY outpatient visit was for measurements of resting energy expenditure (REE) for TR:TREATMENT_SUMMARY the calculation of a weight-maintenance diet (Parvo Medics TrueOne 2400 Canopy TR:TREATMENT_SUMMARY system), DEXA scan (Lunar DPX-L; Lunar Radiation, Madison, WI), and VO2peak test TR:TREATMENT_SUMMARY on a bicycle ergometer (Fig. 1). Participants were admitted to the Clinical TR:TREATMENT_SUMMARY Research Unit (CRU) on the evening of the fifth day of the weight-maintaining TR:TREATMENT_SUMMARY diet provided by the CRU metabolic kitchen (Supplementary Fig. 1). The TR:TREATMENT_SUMMARY weight-maintenance meals (diet composition: 20% protein, 30% fat, 50% TR:TREATMENT_SUMMARY carbohydrate) were monitored daily to ensure that the correct calorie level was TR:TREATMENT_SUMMARY achieved. Upon admission to the CRU, no calories were consumed after 2100 h to TR:TREATMENT_SUMMARY achieve a 10-h fast before the two-stage insulin euglycemic pancreatic clamp the TR:TREATMENT_SUMMARY following morning, as previously published (26), with modifications as follows: TR:TREATMENT_SUMMARY the following morning at 0400 h, a primed [6,62H2]glucose bolus (6 mg ⋅ kg TR:TREATMENT_SUMMARY fat-free mass[FFM]−1) was administered, followed by a 9-h continuous infusion TR:TREATMENT_SUMMARY of [6,62H2]glucose (started at 4 mg ⋅ kgFFM−1 ⋅ h−1 then titrated TR:TREATMENT_SUMMARY downward over the infusion time period to match anticipated changes in TR:TREATMENT_SUMMARY endogenous glucose production [EGP]). At 0600 h, gas exchange was measured by TR:TREATMENT_SUMMARY indirect calorimetry for 30 min for REE determination. Then at 0700 h, glucagon TR:TREATMENT_SUMMARY (0.001 μg ⋅ kgFFM−1 ⋅ min−1), somatostatin (0.093 μg ⋅ kgFFM−1 ⋅ TR:TREATMENT_SUMMARY min−1), and growth hormone (0.0047 μg ⋅ kgFFM−1 ⋅ min−1) were infused TR:TREATMENT_SUMMARY for 6 h. Insulin was infused from 0700 to 1000 h at 0.62 mU ⋅ kgFFM−1 ⋅ TR:TREATMENT_SUMMARY min−1 and then from 1000 to 1300 h at 2.3 mU ⋅ kgFFM−1 ⋅ min−1. A 40% TR:TREATMENT_SUMMARY dextrose with 2% enrichment of [6,62H2]glucose was infused as needed to maintain TR:TREATMENT_SUMMARY blood glucose above 4.7 mmol/L from 0700 to 1000 h and then between 4.7 and 5.3 TR:TREATMENT_SUMMARY mmol/L from 1000 to 1300 h. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY All measurements were made on the second biopsy sample taken after an overnight SP:SAMPLEPREP_SUMMARY fast. Concentrations of amino acids and metabolites were determined using SP:SAMPLEPREP_SUMMARY MassTrak Amino Acid Solution (Waters) modified for mass spectrometry as SP:SAMPLEPREP_SUMMARY previously described (32). Muscle samples were spiked with internal standards SP:SAMPLEPREP_SUMMARY for amino acids and metabolites, deproteinated using cold methanol, and SP:SAMPLEPREP_SUMMARY centrifuged. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY High resolution separation was done using an Acquity UPLC system, injecting 1 CH:CHROMATOGRAPHY_SUMMARY µl of derviatized solution, with a UPLC BEH C18 1.7 micron 2.1×150 mm column CH:CHROMATOGRAPHY_SUMMARY from Waters. Column flow was set to 400 µl/min with a gradient from 99.9%A to CH:CHROMATOGRAPHY_SUMMARY 98%B where buffer A is 1% acetonitrile in 0.1% formic acid and buffer B is 100% CH:CHROMATOGRAPHY_SUMMARY acetonitrile. A column temp of 43 degrees Celsius and a sample tray temp of 6% CH:CHROMATOGRAPHY_SUMMARY Celsius. Mass detection was completed on a TSQ Ultra Quantum from Thermo CH:CHROMATOGRAPHY_SUMMARY Finnigan running in ESI positive mode. A scan width of 0.002, scan time of 0.04 CH:CHROMATOGRAPHY_SUMMARY seconds per transition mass, collision energy of 25, collision gas pressure of CH:CHROMATOGRAPHY_SUMMARY 1.5 mTorr, tube lens value set to 90, monitoring a signature ion of the CH:CHROMATOGRAPHY_SUMMARY derivitized amines at m/z 171.04 by selected reaction monitoring. CH:CHROMATOGRAPHY_TYPE Reversed phase MS:INSTRUMENT_NAME Thermo Quantum Ultra CH:COLUMN_NAME C18 #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:MS_COMMENTS - MS:INSTRUMENT_NAME Thermo Quantum Ultra MS:INSTRUMENT_TYPE Triple quadrupole MS:MS_TYPE ESI MS:ION_MODE POSITIVE #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS micromolar MS_METABOLITE_DATA_START Samples ms5370-1 ms5370-2 ms5370-3 ms5370-4 ms5370-5 ms5370-6 ms5370-7 ms5370-8 ms5370-9 ms5370-10 ms5370-11 ms5370-12 ms5370-13 ms5370-14 ms5370-15 ms5370-16 ms5370-17 ms5370-18 ms5370-19 ms5370-20 ms5370-21 ms5370-22 ms5370-23 ms5370-24 ms5370-25 ms5370-26 ms5370-27 ms5370-28 ms5370-29 ms5370-30 ms5370-31 ms5370-32 ms5370-33 ms5370-34 ms5370-35 ms5370-36 ms5370-37 ms5370-38 ms5370-39 ms5370-40 Factors Time (mins) (mins):1 | Category:Caloric Restriction Time (mins) (mins):2 | Category:Caloric Restriction Time (mins) (mins):1 | Category:Caloric Restriction Time (mins) (mins):2 | Category:Caloric Restriction Time (mins) (mins):1 | Category:Caloric Restriction Time (mins) (mins):2 | Category:Caloric Restriction Time (mins) (mins):1 | Category:Caloric Restriction Time (mins) (mins):2 | Category:Caloric Restriction Time (mins) (mins):1 | Category:Caloric Restriction Time (mins) (mins):2 | Category:Caloric Restriction Time (mins) (mins):1 | Category:Caloric Restriction Time (mins) (mins):2 | Category:Caloric Restriction Time (mins) (mins):1 | Category:Caloric Restriction Time (mins) (mins):2 | Category:Caloric Restriction Time (mins) (mins):1 | Category:Control Time (mins) (mins):2 | Category:Control Time (mins) (mins):1 | Category:Control Time (mins) (mins):2 | Category:Control Time (mins) (mins):1 | Category:Caloric Restriction Time (mins) (mins):2 | Category:Caloric Restriction Time (mins) (mins):1 | Category:Control Time (mins) (mins):2 | Category:Control Time (mins) (mins):1 | Category:Caloric Restriction Time (mins) (mins):2 | Category:Caloric Restriction Time (mins) (mins):1 | Category:Control Time (mins) (mins):2 | Category:Control Time (mins) (mins):1 | Category:Control Time (mins) (mins):2 | Category:Control Time (mins) (mins):1 | Category:Control Time (mins) (mins):2 | Category:Control Time (mins) (mins):1 | Category:Caloric Restriction Time (mins) (mins):2 | Category:Caloric Restriction Time (mins) (mins):1 | Category:Caloric Restriction Time (mins) (mins):2 | Category:Caloric Restriction Time (mins) (mins):1 | Category:Control Time (mins) (mins):2 | Category:Control Time (mins) (mins):1 | Category:Control Time (mins) (mins):2 | Category:Control Time (mins) (mins):1 | Category:Control Time (mins) (mins):2 | Category:Control Histidine 104.5 113.6 264.6 227.9 167.5 101.4 213.6 95.6 135.3 127.1 131.6 134.6 80.4 159.0 180.3 93.1 64.1 60.4 89.7 79.5 193.0 143.1 133.0 144.2 111.9 250.8 135.4 131.6 119.2 69.4 119.4 154.9 94.0 202.5 87.7 81.0 95.2 140.9 137.5 108.2 Hydroxyproline 14.8 20.5 20.6 28.9 19.1 14.7 29.2 39.4 18.4 22.1 24.8 25.5 22.2 27.7 43.5 49.4 16.1 22.5 16.6 28.3 36.6 39.2 40.2 146.7 33.6 76.0 81.3 47.2 27.7 38.3 27.7 66.8 17.9 77.6 27.1 36.7 21.1 27.4 38.0 22.6 1-Methylhistidine 34.7 103.8 142.3 2.0 0.0 0.0 133.2 42.7 70.7 0.0 35.3 52.2 0.0 6.5 0.0 18.5 0.0 42.4 42.1 0.0 57.5 127.5 20.6 0.0 62.3 60.8 88.3 41.0 11.1 0.0 37.9 0.0 16.5 10.9 19.0 1.8 3.4 9.2 26.7 0.0 3-Methylhistidine 7.7 5.7 12.6 5.1 9.0 7.3 18.2 4.7 7.1 12.4 7.0 16.5 3.3 6.9 15.4 2.3 5.2 4.8 1.9 8.6 8.1 4.3 9.5 NF 4.4 8.0 12.4 7.0 8.9 4.9 5.4 8.3 6.9 5.2 9.6 4.1 11.0 5.2 5.5 0.8 Phosphoethanolamine 9.7 11.9 15.9 15.2 12.7 9.9 21.1 43.5 15.2 11.5 14.5 16.0 17.2 13.2 18.2 20.4 12.3 12.0 18.5 33.1 17.3 19.9 17.7 54.9 19.7 31.7 28.9 16.4 8.9 28.6 16.7 30.6 19.4 39.3 11.3 14.1 21.5 16.6 17.5 13.2 Carnosine 2775.1 3167.9 3193.7 4196.9 2613.4 1574.2 2385.6 1376.6 1116.6 741.3 1897.1 1831.9 1332.7 3507.1 5647.8 2611.0 764.5 735.2 1401.6 553.5 2335.8 2229.6 2488.5 2365.0 2278.2 3234.1 4275.4 2304.9 1439.3 683.7 1544.2 3437.7 952.3 1757.3 1437.7 1094.8 896.5 1236.0 2172.9 1228.4 Anserine 48.2 53.3 44.2 67.5 52.3 34.8 42.6 31.7 16.8 9.4 17.1 19.8 19.5 48.6 39.4 34.4 7.1 7.8 15.9 8.5 16.9 20.0 37.1 32.0 16.8 32.2 36.6 22.7 23.0 10.9 13.7 38.9 9.9 21.4 17.1 14.0 6.7 11.7 30.3 15.6 Ethanolamine 19.2 15.7 22.5 22.3 26.2 20.7 29.3 19.6 18.9 15.9 30.3 31.5 18.8 20.2 29.1 18.5 29.5 15.1 23.7 15.1 25.3 22.3 32.6 53.4 32.3 35.0 39.2 42.2 26.4 17.6 16.0 31.4 21.4 32.6 23.6 25.2 23.3 35.3 34.0 27.1 Aspartic Acid 67.7 65.7 70.4 66.1 87.5 37.4 120.3 189.3 25.2 25.5 34.7 39.7 26.6 22.6 72.9 123.2 27.0 36.1 41.9 60.1 70.0 107.7 78.7 129.5 80.7 112.4 66.5 69.4 80.4 125.3 40.5 86.0 20.1 66.9 80.3 65.1 37.9 91.3 25.0 22.6 Sarcosine 1.4 1.4 1.9 1.9 3.0 1.6 3.1 2.1 1.6 1.2 4.3 4.1 2.8 3.9 4.5 4.0 1.8 2.0 2.4 2.2 5.3 3.6 6.2 9.6 5.0 7.1 8.5 6.4 2.5 1.9 3.4 4.2 2.0 4.2 3.6 3.2 2.2 4.3 4.4 2.4 beta-Alanine 39.2 50.7 52.7 67.9 57.1 36.3 74.6 111.1 51.8 83.4 54.8 39.2 68.4 92.9 157.9 76.0 33.6 26.6 52.0 55.6 81.1 69.8 62.7 129.7 35.0 103.5 71.6 79.8 36.5 55.9 46.3 52.3 63.9 89.0 24.7 13.6 58.7 66.0 41.4 54.2 gamma-Amino-N-butyric-acid 1.6 0.7 1.2 1.0 1.4 0.6 1.9 11.2 1.1 0.4 0.7 1.0 1.2 0.5 0.9 1.4 0.4 0.5 0.5 1.1 0.6 1.5 1.1 2.7 0.9 1.7 1.7 1.3 1.1 5.6 0.7 1.7 1.4 3.7 1.3 2.3 0.6 0.9 2.2 1.0 alpha-Aminoadipic-acid 10.8 7.1 14.5 30.5 7.2 4.9 53.8 11.7 13.5 12.2 18.4 20.3 11.8 16.0 10.5 5.3 6.2 13.2 23.6 39.6 34.8 26.1 17.6 13.9 11.1 27.0 3.6 9.7 10.8 19.3 24.2 25.8 24.8 44.4 16.0 21.2 28.3 29.3 11.5 20.5 beta-Aminoisobutyric-acid 0.8 0.6 1.5 1.9 0.9 0.3 1.0 4.7 0.8 1.2 0.7 1.2 1.6 0.6 2.0 2.6 0.7 0.7 0.8 0.8 0.6 1.6 1.0 3.2 0.7 1.4 2.1 1.5 2.5 6.3 1.0 2.3 1.3 2.7 0.3 0.9 2.0 2.4 1.8 2.7 Hydroxylysine 1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Hydroxylysine 2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 alpha-Amino-N-butyric-acid 19.3 25.6 17.2 17.2 30.1 17.8 36.2 84.0 12.4 8.3 26.8 25.9 18.9 22.5 44.6 63.1 12.4 12.1 24.3 24.8 52.6 43.1 40.5 57.6 36.4 65.9 56.6 52.6 33.2 39.0 23.6 65.2 24.3 48.8 28.1 21.9 28.4 37.4 39.4 28.2 Cystathionine 1 2.3 1.4 2.0 0.8 4.8 0.8 8.6 0.8 0.6 0.0 10.6 4.7 1.0 0.0 0.0 2.5 0.2 0.1 0.0 0.1 5.8 1.6 8.2 2.3 1.6 1.4 0.2 1.0 1.3 0.3 0.8 1.1 2.6 2.1 2.6 2.7 3.9 1.8 0.3 0.0 Cystathionine 2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Methionine 16.3 14.3 17.2 15.7 26.0 13.6 24.5 41.3 15.7 16.6 26.2 17.1 16.0 23.4 24.9 31.0 13.3 15.1 17.0 18.0 31.6 40.9 44.4 67.9 26.4 30.2 34.5 30.8 35.2 36.4 22.3 23.3 29.0 36.5 27.0 25.3 19.9 25.3 40.6 46.8 allo-Isoleucine 1.1 0.9 0.6 0.0 1.5 0.3 1.3 0.0 0.0 0.0 2.4 1.3 0.7 1.1 2.4 1.7 0.4 0.5 0.0 0.0 0.0 0.0 1.6 0.0 1.6 1.6 1.6 1.3 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 1.1 0.0 Homocystine 0.4 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Asparagine 135.8 109.6 95.3 105.1 120.2 83.4 180.6 221.2 92.6 83.0 161.9 130.8 93.1 98.3 145.2 146.3 76.6 101.8 141.6 140.1 179.5 161.8 194.0 287.3 133.8 210.3 139.9 156.1 167.7 180.7 120.6 218.2 138.5 217.7 135.6 125.6 107.7 158.5 200.2 231.4 Arginine 319.5 364.0 549.8 551.7 318.7 199.6 322.4 131.3 223.9 115.8 429.4 261.4 91.9 141.6 183.8 152.1 180.0 219.0 232.4 119.9 271.2 291.7 353.1 318.1 161.3 238.0 194.3 240.5 323.0 205.4 272.1 228.4 322.4 415.2 284.2 241.6 278.9 479.8 323.2 330.1 Taurine 3807.6 4395.3 4577.4 5475.9 3375.9 2971.8 5424.9 6274.0 3620.2 3661.3 4115.4 4032.6 3161.4 3654.8 6381.9 5429.2 2765.7 3164.0 4796.8 4781.0 5524.5 5626.5 3519.5 6201.7 5805.5 6758.2 7663.7 5853.0 3008.1 4118.4 3051.8 6625.7 3709.5 7280.3 3039.0 2346.1 6344.1 6909.3 8552.6 5367.7 Serine 155.9 176.1 120.9 199.2 119.2 101.2 246.3 444.9 126.5 173.5 198.5 154.3 156.8 206.1 158.9 216.4 88.8 116.2 177.4 246.1 319.1 336.1 224.3 427.8 158.1 289.3 140.1 151.9 169.3 236.3 175.0 344.9 196.1 359.2 189.9 186.4 185.7 274.2 346.4 344.5 Glutamine 9953.2 9168.1 10737.0 10435.5 11559.8 6802.0 11255.2 3880.7 10262.4 5866.4 8863.2 8335.1 4780.2 7309.8 9135.0 6076.2 5763.1 6278.0 7828.0 6773.4 10533.2 9982.0 10921.4 7956.1 10770.4 12941.6 11927.9 12901.2 6252.3 4083.2 8327.0 11250.6 8380.8 14246.3 8376.1 6047.6 9755.6 13998.4 14552.4 7752.3 Glycine 520.6 504.4 531.7 758.3 544.5 393.8 643.3 1119.7 867.5 769.6 543.8 550.9 603.7 764.0 700.5 776.4 379.0 379.2 1035.7 1163.6 803.1 711.7 662.8 1386.7 830.5 1256.3 957.0 779.2 612.9 736.1 454.2 919.6 559.5 1049.4 634.8 588.1 548.7 782.1 1424.1 890.8 Citrulline 28.5 27.7 48.5 33.0 88.7 25.3 63.9 10.6 264.7 82.4 299.9 314.1 67.4 142.6 244.7 187.7 63.8 69.9 38.5 36.5 105.3 100.7 250.4 172.3 159.6 201.4 370.2 356.1 149.8 65.5 140.0 66.5 62.0 60.3 191.3 82.1 145.7 215.5 77.4 60.0 Glutamic Acid 1726.9 1073.0 1774.1 1497.5 1192.7 611.7 2552.3 1598.8 1076.7 728.7 1304.8 1263.2 805.4 835.9 1574.7 1351.1 746.6 991.0 925.8 670.3 1681.5 1659.5 1727.6 2613.7 1129.7 1714.7 1930.6 1604.4 844.1 998.4 1022.1 1662.2 1450.2 1891.3 971.1 1057.4 1195.9 1571.0 2001.8 1705.6 Threonine 177.5 168.3 176.5 293.3 240.2 155.3 269.6 418.1 145.3 129.4 242.3 204.1 175.6 202.0 355.1 375.3 139.0 178.6 236.2 228.9 303.8 344.0 344.1 677.5 307.2 471.2 381.9 319.2 254.2 318.1 241.4 382.6 191.9 327.2 302.0 245.9 270.4 377.0 336.2 426.0 Alanine 1250.8 1516.8 1193.4 1461.8 1206.2 845.4 1914.7 1832.6 1177.3 833.3 1733.9 1416.1 1160.2 1335.5 2047.7 1802.9 813.8 1012.1 1579.4 1005.0 2476.1 2257.6 1917.5 2321.8 2355.5 2829.6 2947.9 2866.2 1616.8 1502.1 1384.7 2254.0 1445.7 2386.7 1460.8 1012.7 1738.7 2299.6 2271.8 1895.9 Proline 263.3 231.5 203.1 209.7 313.6 168.0 494.0 484.6 220.5 192.9 369.9 351.2 224.8 263.8 540.1 572.3 163.4 213.3 272.0 255.9 520.0 491.9 436.6 607.9 470.9 735.3 705.9 491.4 365.2 357.3 401.1 563.3 270.1 569.4 322.7 359.2 392.0 515.3 306.4 304.8 Ornithine 101.8 118.3 166.6 193.7 112.4 52.1 129.2 44.0 87.4 73.3 101.2 83.6 44.7 71.6 82.1 56.2 49.0 91.8 102.4 92.0 198.1 129.5 85.8 73.7 74.6 108.4 92.5 108.1 75.8 45.1 108.9 156.9 69.2 166.5 135.4 169.2 124.3 237.2 138.0 79.4 Lysine 732.2 870.7 1405.9 1369.4 749.5 477.0 1154.4 320.4 556.7 323.2 969.2 621.1 223.2 517.6 453.9 246.1 405.1 615.7 482.4 252.5 676.6 912.3 927.7 657.6 405.3 640.6 591.3 553.9 603.8 367.3 612.1 677.7 749.8 1143.0 492.9 547.0 762.0 1182.7 864.6 893.4 Cystine 0.1 0.0 0.2 0.0 0.1 0.1 0.0 0.2 0.0 0.4 0.1 0.0 0.3 0.0 0.0 0.0 0.2 0.0 0.0 0.3 0.0 0.0 0.1 0.2 0.0 0.0 0.0 0.0 0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.1 0.0 0.1 0.0 0.0 Tyrosine 40.0 33.6 38.2 34.4 57.1 29.2 44.8 59.4 25.2 29.9 59.6 35.7 40.5 58.1 60.7 68.0 20.7 22.0 31.5 32.9 64.0 75.9 76.1 122.3 42.6 59.8 71.1 62.9 53.8 51.5 47.2 52.7 67.7 87.9 61.7 51.4 33.4 49.9 63.8 80.3 Valine 139.5 130.0 133.7 109.6 154.8 84.2 194.3 173.1 111.1 103.3 206.3 170.9 106.1 164.0 205.5 210.0 74.8 89.1 85.6 87.3 193.2 208.8 223.7 279.9 167.5 252.1 194.6 167.2 178.4 172.2 124.4 159.6 167.1 235.5 185.0 146.4 142.3 173.2 183.5 176.7 Isoleucine 28.7 29.3 31.0 20.9 41.5 16.5 51.4 53.1 22.5 24.1 48.0 28.6 19.0 30.6 38.4 38.8 19.3 21.2 18.4 21.1 41.4 57.0 64.8 77.0 28.8 42.1 37.9 34.9 45.9 52.3 27.1 31.3 44.5 50.6 42.4 36.3 25.6 35.3 43.7 67.1 Leucine 79.9 76.6 83.4 69.5 98.5 44.7 124.9 146.0 65.3 70.4 125.7 84.4 65.5 106.5 120.8 137.4 51.7 59.2 55.5 67.9 125.7 162.7 157.1 246.3 100.3 147.3 117.0 106.8 122.5 134.9 87.8 92.6 114.0 149.9 119.1 104.2 80.8 109.4 120.8 134.4 Phenylalanine 36.7 39.0 39.8 38.6 49.6 26.9 63.8 72.3 34.2 41.8 60.9 37.8 34.6 55.7 65.1 66.5 27.6 30.9 35.4 40.1 69.6 83.6 68.4 117.4 45.9 64.2 62.2 61.9 61.4 58.5 49.8 56.5 66.8 84.4 55.4 46.2 42.5 60.8 71.9 69.2 Tryptophan 7.9 8.4 10.3 9.4 11.5 6.8 12.7 15.3 8.1 8.1 13.1 8.6 8.0 14.3 13.8 13.0 6.2 6.5 7.9 9.0 16.6 21.6 19.0 25.2 9.7 14.3 17.1 15.7 13.7 13.4 12.5 12.5 12.8 19.5 14.1 10.7 10.3 16.5 16.4 13.7 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Histidine Hydroxyproline 1-Methylhistidine 3-Methylhistidine Phosphoethanolamine Carnosine Anserine Ethanolamine Aspartic Acid Sarcosine beta-Alanine gamma-Amino-N-butyric-acid alpha-Aminoadipic-acid beta-Aminoisobutyric-acid Hydroxylysine 1 Hydroxylysine 2 alpha-Amino-N-butyric-acid Cystathionine 1 Cystathionine 2 Methionine allo-Isoleucine Homocystine Asparagine Arginine Taurine Serine Glutamine Glycine Citrulline Glutamic Acid Threonine Alanine Proline Ornithine Lysine Cystine Tyrosine Valine Isoleucine Leucine Phenylalanine Tryptophan METABOLITES_END #END