#METABOLOMICS WORKBENCH hormel101_20170623_144136 DATATRACK_ID:1097 STUDY_ID:ST000648 ANALYSIS_ID:AN000980 PROJECT_ID:PR000460
VERSION             	1
CREATED_ON             	June 26, 2017, 8:06 am
#PROJECT
PR:PROJECT_TITLE                 	The dystrophic muscle metabolome: effects of exercise and NO donor therapy
PR:PROJECT_SUMMARY               	"In Duchenne and Becker muscular dystrophy (DMD, BMD), loss of the cytoskeletal
PR:PROJECT_SUMMARY               	protein dystrophin weakens the sarcolemma and disrupts cellular signaling,
PR:PROJECT_SUMMARY               	rendering the diseased muscles susceptible to contractioninduced damage. We and
PR:PROJECT_SUMMARY               	others have shown that loss of neuronal nitric oxide synthase (nNOSμ) from the
PR:PROJECT_SUMMARY               	sarcolemma of dystrophin-deficient muscle causes functional muscle ischemia
PR:PROJECT_SUMMARY               	during exercise due to unopposed sympathetic vasoconstriction, thereby
PR:PROJECT_SUMMARY               	exacerbating fatigue and injury of the diseased muscles. Genetic and
PR:PROJECT_SUMMARY               	pharmacologic strategies targeting nNOSμ-NO signaling ameliorate functional
PR:PROJECT_SUMMARY               	muscle ischemia, as well as many other features of the dystrophic phenotype in
PR:PROJECT_SUMMARY               	the mdx mouse model of DMD/BMD. These findings suggest that the therapeutic
PR:PROJECT_SUMMARY               	benefit of NO likely extends beyond its vascular effects. A growing body of
PR:PROJECT_SUMMARY               	evidence indicates that NO directly influences muscle metabolism through effects
PR:PROJECT_SUMMARY               	on glucose transport as well as mitochondrial biogenesis and function. Both
PR:PROJECT_SUMMARY               	nNOS-/- mice and mdx mice exhibit muscle mitochondrial dysfunction, decreased
PR:PROJECT_SUMMARY               	resistance to fatigue, and exercise-induced muscle injury, suggesting a causal
PR:PROJECT_SUMMARY               	role of nNOSμ-NO deficiency. However, the specific metabolic changes resulting
PR:PROJECT_SUMMARY               	from reduced NO signaling that might render dystrophic muscle susceptible to
PR:PROJECT_SUMMARY               	fatigue and use-dependent injury remain poorly defined. Therefore, the goal of
PR:PROJECT_SUMMARY               	this pilot metabolomics study is to identify the unique biochemical profiles of
PR:PROJECT_SUMMARY               	skeletal and cardiac muscles of mdx mice to gain further mechanistic insight
PR:PROJECT_SUMMARY               	into the pathophysiological role of NO deficiency in muscular dystrophy. In Aim
PR:PROJECT_SUMMARY               	1, we will characterize the skeletal and cardiac muscle metabolomes of mdx and
PR:PROJECT_SUMMARY               	nNOS-/- mice at rest and following a single bout of treadmill exercise with the
PR:PROJECT_SUMMARY               	goal of discovering common metabolic signatures caused by loss of NO signaling.
PR:PROJECT_SUMMARY               	In Aim 2, we will evaluate the potential of a NO donor drug that is under
PR:PROJECT_SUMMARY               	development as a therapeutic for DMD/BMD to improve the skeletal and cardiac
PR:PROJECT_SUMMARY               	muscle metabolomes in mdx mice. As a result of this pilot study, we hope to gain
PR:PROJECT_SUMMARY               	new understanding of the metabolic derangements in dystrophin-deficient muscle,
PR:PROJECT_SUMMARY               	insight into the therapeutic effects of NO replacement, and to identify new
PR:PROJECT_SUMMARY               	pathogenic mechanisms and putative therapeutic targets that will form the basis
PR:PROJECT_SUMMARY               	of future grant applications."
PR:INSTITUTE                     	Mayo Clinic
PR:LAST_NAME                     	Thomas
PR:FIRST_NAME                    	Gail
PR:ADDRESS                       	Penn State Hershey Heart and Vascular Institute Penn State College of Medicine
PR:ADDRESS                       	500 University Drive, MC H047 Hershey, PA 17033
PR:EMAIL                         	gthomas4@hmc.psu.edu
PR:PHONE                         	717-531-0003, ext. 287087
#STUDY
ST:STUDY_TITLE                   	Effects of NO Donor Therapy on the Dystrophic Mouse Muscle Amino Acids (part IV)
ST:STUDY_SUMMARY                 	For this aim, we will only use male mdx mice. We will study three groups treated
ST:STUDY_SUMMARY                 	for 7 days with vehicle, naproxcinod (i.e., NO-naproxen), or naproxen (n = 10
ST:STUDY_SUMMARY                 	each group). Two hours after the final treatment, half the mice in each group
ST:STUDY_SUMMARY                 	will be run to exhaustion on a treadmill. The heart and gastrocnemius, soleus,
ST:STUDY_SUMMARY                 	and quadriceps muscles of one hindlimb will be sent to the Mayo Clinic
ST:STUDY_SUMMARY                 	Metabolomics Resource Core. The heart and quadriceps muscle will be used for
ST:STUDY_SUMMARY                 	untargeted metabolomics profiling (LC/MS) while the gastrocnemius and soleus
ST:STUDY_SUMMARY                 	muscles will be used for targeted analyses of amino acids plus amino
ST:STUDY_SUMMARY                 	metabolites, non-esterified fatty acids, and citric acid cycle intermediates.
ST:INSTITUTE                     	Mayo Clinic
ST:LAST_NAME                     	Thomas
ST:FIRST_NAME                    	Gail
ST:ADDRESS                       	Penn State Hershey Heart and Vascular Institute Penn State College of Medicine
ST:ADDRESS                       	500 University Drive, MC H047 Hershey, PA 17033
ST:EMAIL                         	gthomas4@hmc.psu.edu
ST:PHONE                         	717-531-0003, ext. 287087
#SUBJECT
SU:SUBJECT_TYPE                  	Mouse
SU:SUBJECT_SPECIES               	Mus musculus
SU:TAXONOMY_ID                   	10090
#SUBJECT_SAMPLE_FACTORS:         	SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data
SUBJECT_SAMPLE_FACTORS           	-	ms5862-1	Time point:Sedentary | Grouping:SED-Naproxcinod	Date of study=9/23/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-2	Time point:Sedentary | Grouping:SED-Naproxcinod	Date of study=9/24/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-3	Time point:Sedentary | Grouping:SED-Naproxcinod	Date of study=10/1/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-4	Time point:Sedentary | Grouping:SED-Naproxcinod	Date of study=10/7/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-5	Time point:Sedentary | Grouping:SED-Naproxcinod	Date of study=10/9/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-6	Time point:Post Run | Grouping:RUN-Naproxcinod	Date of study=9/23/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-7	Time point:Post Run | Grouping:RUN-Naproxcinod	Date of study=9/24/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-8	Time point:Post Run | Grouping:RUN-Naproxcinod	Date of study=10/1/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-9	Time point:Post Run | Grouping:RUN-Naproxcinod	Date of study=10/7/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-10	Time point:Post Run | Grouping:RUN-Naproxcinod	Date of study=10/9/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-11	Time point:Sedentary | Grouping:SED-Naproxen	Date of study=9/23/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-12	Time point:Sedentary | Grouping:SED-Naproxen	Date of study=9/24/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-13	Time point:Sedentary | Grouping:SED-Naproxen	Date of study=10/1/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-14	Time point:Sedentary | Grouping:SED-Naproxen	Date of study=10/7/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-15	Time point:Sedentary | Grouping:SED-Naproxen	Date of study=10/9/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-16	Time point:Post Run | Grouping:RUN-Naproxen	Date of study=9/23/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-17	Time point:Post Run | Grouping:RUN-Naproxen	Date of study=9/24/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-18	Time point:Post Run | Grouping:RUN-Naproxen	Date of study=10/1/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-19	Time point:Post Run | Grouping:RUN-Naproxen	Date of study=10/7/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-20	Time point:Post Run | Grouping:RUN-Naproxen	Date of study=10/9/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-21	Time point:Sedentary | Grouping:SED-Vehicle	Date of study=9/23/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-22	Time point:Sedentary | Grouping:SED-Vehicle	Date of study=9/24/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-23	Time point:Sedentary | Grouping:SED-Vehicle	Date of study=10/1/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-24	Time point:Sedentary | Grouping:SED-Vehicle	Date of study=10/7/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-25	Time point:Sedentary | Grouping:SED-Vehicle	Date of study=10/9/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-26	Time point:Post Run | Grouping:RUN-Vehicle	Date of study=9/23/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-27	Time point:Post Run | Grouping:RUN-Vehicle	Date of study=9/24/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-28	Time point:Post Run | Grouping:RUN-Vehicle	Date of study=10/1/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-29	Time point:Post Run | Grouping:RUN-Vehicle	Date of study=10/7/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
SUBJECT_SAMPLE_FACTORS           	-	ms5862-30	Time point:Post Run | Grouping:RUN-Vehicle	Date of study=10/9/2015; Gender=Male; Sample type=Tissue-Gastrocnemius; Species=Mouse
#COLLECTION
CO:COLLECTION_SUMMARY            	Blood and Tissue Harvesting: Mice will be euthanized and blood will be taken by
CO:COLLECTION_SUMMARY            	cardiac puncture, centrifuged, and the plasma will be stored at -80ºC. The
CO:COLLECTION_SUMMARY            	heart, diaphragm, and muscles of both hindlimbs (gastrocnemius, soleus,
CO:COLLECTION_SUMMARY            	quadriceps) will be dissected and snap frozen in liquid nitrogen. Tibialis
CO:COLLECTION_SUMMARY            	anterior and plantaris muscles from both hindlimbs also will be dissected and
CO:COLLECTION_SUMMARY            	one set will be snap frozen in liquid nitrogen while the other set will be
CO:COLLECTION_SUMMARY            	mounted in OCT and frozen in isopentane cooled by liquid nitrogen. Cryosections
CO:COLLECTION_SUMMARY            	will be used to evaluate disease activity and exercise-induced muscle injury by
CO:COLLECTION_SUMMARY            	staining with: (a) hematoxylin and eosin to assess gross morphology, cellular
CO:COLLECTION_SUMMARY            	infiltration, and necrosis, (b) anti-F4/80 to label macrophages, and (c)
CO:COLLECTION_SUMMARY            	anti-IgG or IgM to label damaged muscle fibers.
#TREATMENT
TR:TREATMENT_SUMMARY             	"Studies will be performed in 12-16 week old male mdx mice, C57BL10 control
TR:TREATMENT_SUMMARY             	mice, and nNOS-/- mice obtained from Jackson Laboratory. All protocols will be
TR:TREATMENT_SUMMARY             	approved by the Penn State College of Medicine Institutional Animal Care and Use
TR:TREATMENT_SUMMARY             	Committee. Drug Treatment: Mice will be treated with vehicle, naproxcinod (20
TR:TREATMENT_SUMMARY             	mg/kg/day) or equimolar naproxen (12.5mg/kg/day) once a day for 7 consecutive
TR:TREATMENT_SUMMARY             	days. To avoid the stress of oral gavage or ip injections in mdx mice, drug or
TR:TREATMENT_SUMMARY             	vehicle will be administered in a small volume of peanut butter. Most mice
TR:TREATMENT_SUMMARY             	readily consume the dosed peanut butter within 30 min. Terminal experiments will
TR:TREATMENT_SUMMARY             	be performed 2 hours after the final dose is consumed."
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	mouse gastrocnemius amino acids
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_TYPE           	Reversed phase
CH:INSTRUMENT_NAME               	Waters Acquity
CH:COLUMN_NAME                   	Waters Acquity BEH C18 (150 x 2.1mm, 1.7um)
#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         	picomoles/mg
MS_METABOLITE_DATA_START
Samples	ms5862-1	ms5862-2	ms5862-3	ms5862-4	ms5862-5	ms5862-6	ms5862-7	ms5862-8	ms5862-9	ms5862-10	ms5862-11	ms5862-12	ms5862-13	ms5862-14	ms5862-15	ms5862-16	ms5862-17	ms5862-18	ms5862-19	ms5862-20	ms5862-21	ms5862-22	ms5862-23	ms5862-24	ms5862-25	ms5862-26	ms5862-27	ms5862-28	ms5862-29	ms5862-30
Factors	Time point:Sedentary | Grouping:SED-Naproxcinod	Time point:Sedentary | Grouping:SED-Naproxcinod	Time point:Sedentary | Grouping:SED-Naproxcinod	Time point:Sedentary | Grouping:SED-Naproxcinod	Time point:Sedentary | Grouping:SED-Naproxcinod	Time point:Post Run | Grouping:RUN-Naproxcinod	Time point:Post Run | Grouping:RUN-Naproxcinod	Time point:Post Run | Grouping:RUN-Naproxcinod	Time point:Post Run | Grouping:RUN-Naproxcinod	Time point:Post Run | Grouping:RUN-Naproxcinod	Time point:Sedentary | Grouping:SED-Naproxen	Time point:Sedentary | Grouping:SED-Naproxen	Time point:Sedentary | Grouping:SED-Naproxen	Time point:Sedentary | Grouping:SED-Naproxen	Time point:Sedentary | Grouping:SED-Naproxen	Time point:Post Run | Grouping:RUN-Naproxen	Time point:Post Run | Grouping:RUN-Naproxen	Time point:Post Run | Grouping:RUN-Naproxen	Time point:Post Run | Grouping:RUN-Naproxen	Time point:Post Run | Grouping:RUN-Naproxen	Time point:Sedentary | Grouping:SED-Vehicle	Time point:Sedentary | Grouping:SED-Vehicle	Time point:Sedentary | Grouping:SED-Vehicle	Time point:Sedentary | Grouping:SED-Vehicle	Time point:Sedentary | Grouping:SED-Vehicle	Time point:Post Run | Grouping:RUN-Vehicle	Time point:Post Run | Grouping:RUN-Vehicle	Time point:Post Run | Grouping:RUN-Vehicle	Time point:Post Run | Grouping:RUN-Vehicle	Time point:Post Run | Grouping:RUN-Vehicle
Histidine	103.7	109.7	85.7	70.7	118.7	96.3	106.4	85.8	109.7	74.5	115.7	171.0	101.0	105.2	126.9	95.1	99.3	82.9	84.2	117.9	121.4	135.2	78.7	194.8	117.8	150.9	102.9	77.2	130.8	85.1
Hydroxyproline	73.0	87.6	81.0	64.3	110.6	79.0	84.8	66.3	139.1	66.6	87.3	129.8	101.1	85.1	113.0	48.4	109.5	43.9	56.8	50.1	101.1	76.1	77.1	90.9	92.3	73.9	78.8	81.9	198.7	119.2
1-Methylhistidine	4.3	3.5	1.5	1.7	11.6	8.2	4.7	2.3	9.5	5.7	4.2	7.5	2.9	2.1	4.8	2.0	2.3	3.3	1.7	7.2	2.4	7.0	2.3	8.6	3.9	2.3	4.6	1.7	3.0	2.2
3-Methylhistidine	5.8	3.9	3.5	4.5	8.8	6.1	3.6	4.0	5.8	4.8	5.2	6.2	4.4	3.1	8.2	3.3	2.9	4.7	5.6	2.9	5.7	5.5	4.2	4.3	6.6	2.5	3.0	4.6	8.3	3.5
Asparagine	48.0	40.8	35.4	32.3	54.7	40.6	49.2	39.7	42.4	30.2	54.4	56.5	44.0	51.5	53.5	31.8	41.9	40.5	38.2	42.6	45.6	50.8	33.7	72.8	51.2	56.6	45.5	38.1	56.5	36.7
Phosphoethanolamine	12.5	11.1	13.6	7.6	17.1	17.4	25.2	12.8	17.2	15.8	12.1	13.4	12.6	26.0	14.4	11.7	13.6	16.8	18.2	12.6	13.8	11.9	14.4	14.6	17.5	13.5	12.9	16.3	17.5	12.4
Arginine	88.0	126.8	77.7	77.4	104.4	85.5	86.6	79.1	93.0	92.0	89.8	169.1	98.7	75.9	193.0	67.8	125.0	67.0	81.3	133.7	100.9	93.7	91.5	272.4	135.4	148.5	71.4	111.3	192.6	130.3
Carnosine	1352.8	1195.1	1066.8	1304.0	1213.0	963.8	1086.7	923.5	1083.6	1023.6	1336.4	1373.7	1277.6	826.9	1205.0	700.7	1174.8	721.3	1004.7	873.3	1392.6	972.1	847.6	1362.4	983.4	1240.8	1241.0	1091.4	1193.0	1150.4
Taurine	10459.7	11611.0	9896.7	10278.8	11240.8	9994.7	11029.1	9812.5	10093.3	7420.7	12218.4	9135.9	11124.4	8574.6	12506.4	5489.8	9075.5	7085.2	10273.9	10336.3	11362.1	10027.4	7100.7	15894.1	9828.9	12848.9	9650.1	8807.8	11354.7	8383.6
Anserine	1463.5	1218.0	889.0	1320.1	1272.2	1050.0	1015.2	986.9	977.6	941.6	1431.4	1092.0	1348.4	689.7	1321.6	582.1	913.1	709.0	921.3	937.2	1225.6	877.0	703.5	1716.2	809.3	1253.5	952.7	694.4	958.0	758.2
Serine	124.3	139.8	112.5	96.3	134.5	103.2	133.7	103.1	107.9	94.3	159.4	158.3	142.2	168.2	142.5	71.5	107.4	87.5	90.4	160.5	151.6	151.6	100.7	195.3	120.3	170.6	108.9	102.2	157.3	107.4
Glutamine	697.0	828.4	768.8	620.1	807.7	756.6	1100.8	546.9	635.6	554.0	910.1	782.4	835.2	713.2	878.1	508.1	622.8	488.3	572.6	703.0	830.7	798.3	584.7	1201.8	664.5	954.2	697.8	566.9	838.4	595.6
Ethanolamine	16.9	12.1	12.0	12.5	14.7	15.9	16.9	14.6	13.4	19.2	12.7	14.3	12.7	13.1	12.2	8.4	12.8	13.6	13.4	15.1	17.0	13.8	7.8	24.0	13.6	21.2	14.3	11.4	13.2	9.4
Glycine	973.4	1113.4	1120.8	863.3	1307.4	937.6	1253.5	781.1	1352.7	835.8	1245.0	1335.9	1186.1	1178.1	1230.8	736.5	1091.3	677.7	775.3	858.7	1225.4	1138.0	849.2	1150.0	978.1	1117.0	814.1	887.2	1660.8	1114.5
Aspartic Acid	52.5	80.1	69.3	25.7	56.2	65.3	57.6	56.0	49.4	25.9	81.9	71.0	57.5	78.6	47.1	73.2	38.9	44.3	57.4	64.1	66.4	74.8	44.0	64.5	72.6	61.2	44.8	40.7	80.7	41.0
Sarcosine	2.1	3.2	2.6	2.0	2.2	2.1	2.9	1.0	2.9	1.6	1.7	3.8	2.2	2.7	2.6	1.0	2.7	0.9	1.2	2.6	1.9	3.1	1.6	3.8	1.7	1.9	1.7	1.3	3.7	2.6
Citrulline	50.9	79.0	73.4	51.4	69.1	60.5	70.2	47.6	57.8	45.3	68.3	90.0	69.2	56.1	80.4	39.8	51.4	34.0	49.1	60.3	79.0	69.2	39.0	90.9	49.8	71.9	48.0	43.6	73.7	60.0
Glutamic Acid	267.2	321.4	365.3	222.0	351.7	323.2	378.2	325.8	341.9	211.9	439.1	342.6	347.9	472.5	305.5	282.5	362.7	230.9	284.1	349.3	332.5	370.9	222.2	559.5	280.2	334.1	336.5	218.4	464.6	272.3
beta-Alanine	28.0	25.3	23.8	26.3	30.7	24.6	27.4	20.4	35.7	16.6	23.4	25.6	31.7	18.1	25.5	10.5	27.3	13.6	25.5	15.6	32.7	17.7	21.3	23.4	21.6	23.5	35.4	29.2	29.7	41.4
Threonine	95.9	115.4	104.2	82.4	129.2	91.5	112.2	79.2	99.3	80.2	125.8	140.9	103.1	123.8	140.7	66.2	103.5	71.6	79.6	100.4	135.3	109.6	73.7	144.3	120.9	126.0	103.7	99.3	156.7	101.9
Alanine	869.2	1146.3	903.5	831.6	1163.3	924.8	1038.6	882.9	874.3	596.9	1116.3	1246.8	1113.9	800.8	1339.6	666.1	1050.0	665.5	909.4	978.3	995.3	992.7	776.7	1664.4	1065.1	1026.7	825.7	725.2	1241.4	838.8
gamma-Amino-N-butyric-acid	0.78	0.71	0.84	0.85	0.97	0.94	1.23	1.38	1.08	0.44	1.20	0.93	1.30	0.82	1.40	0.53	1.05	0.80	0.93	1.19	0.87	1.05	0.64	1.76	0.77	1.41	0.77	0.68	1.23	0.68
alpha-Aminoadipic-acid	1.4	1.2	1.6	1.2	1.3	1.6	1.5	1.3	2.8	1.0	1.6	1.7	1.3	1.7	1.7	0.7	1.7	1.3	1.1	3.1	1.4	1.2	1.7	3.3	2.4	1.6	1.2	1.8	2.5	1.6
beta-Aminoisobutyric-acid	0.0	0.0	0.1	0.1	0.1	0.1	0.1	0.1	0.1	0.1	0.1	0.1	0.1	0.1	0.1	0.0	0.1	0.1	0.1	0.1	0.2	0.1	0.0	0.2	0.1	0.1	0.1	0.0	0.1	0.1
Proline	74.4	94.7	77.0	66.7	97.7	69.6	89.2	75.9	88.8	63.2	78.5	112.2	86.4	109.5	99.3	57.3	106.2	63.8	68.4	84.1	94.8	105.1	66.5	124.0	97.3	94.2	84.1	72.9	142.0	112.0
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
Hydroxylysine 2	0.2	0.2	0.2	0.1	0.3	0.3	0.3	0.2	0.3	0.3	0.2	0.3	0.3	0.3	0.4	0.2	0.4	0.2	0.2	0.2	0.2	0.2	0.3	0.2	0.3	0.2	0.2	0.3	0.5	0.3
alpha-Amino-N-butyric-acid	1.0	1.8	1.6	1.0	1.8	1.2	1.4	1.0	1.4	0.9	1.5	2.4	1.6	1.8	2.2	1.0	2.2	1.1	1.0	1.3	1.7	1.9	1.2	1.9	1.8	1.4	1.4	1.4	2.1	1.6
Ornithine	15.8	27.6	15.3	14.8	14.8	16.4	14.5	17.4	14.6	16.9	18.2	24.0	21.0	32.2	30.5	8.8	18.9	10.8	12.8	26.9	16.6	23.1	13.1	25.9	12.9	17.9	12.5	14.0	21.3	17.6
Cystathionine 1	3.6	2.4	1.7	2.1	2.1	2.8	1.8	2.3	2.4	1.9	3.8	3.4	2.4	2.6	5.4	1.2	2.5	1.4	2.3	1.9	3.1	3.5	1.1	4.2	2.7	2.6	2.3	1.9	3.7	2.3
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
Lysine	234.5	282.1	175.8	175.4	220.4	214.4	226.8	150.5	191.1	208.2	267.8	362.6	229.1	153.9	462.3	150.8	324.5	146.4	181.0	305.5	249.1	226.2	188.5	567.8	320.2	353.3	196.2	246.0	404.7	236.7
Cystine	13.6	11.0	12.6	9.3	14.3	11.3	10.7	11.9	20.3	11.5	12.5	13.7	11.5	18.5	13.6	10.5	13.6	18.6	14.2	11.8	11.4	16.5	9.0	12.4	17.6	17.0	12.6	11.0	20.3	10.6
Tyrosine	40.8	34.3	36.6	39.3	42.1	42.2	46.1	44.8	54.5	32.5	41.8	38.3	45.8	43.3	45.7	24.6	37.3	43.0	52.2	40.4	37.0	37.7	22.8	60.5	47.4	64.6	41.4	50.9	70.0	44.6
Methionine	27.7	35.0	29.5	21.7	38.3	28.8	32.8	26.5	34.9	23.8	29.4	46.9	29.8	37.4	42.5	15.9	31.1	25.6	29.5	28.4	37.0	35.7	19.1	52.7	40.3	40.9	32.8	31.6	46.9	33.8
Valine	89.7	74.2	69.0	56.7	85.8	69.3	90.4	80.0	93.6	55.5	69.8	89.7	76.7	90.0	85.4	52.4	73.2	73.7	72.9	76.5	73.1	82.3	40.7	107.5	77.9	104.3	81.0	79.2	110.2	74.3
Isoleucine	39.3	25.2	28.9	23.4	37.8	27.5	33.1	33.2	39.2	24.5	25.2	36.6	33.1	38.1	34.8	22.7	27.0	37.7	34.0	33.7	28.4	38.0	18.1	53.9	39.5	41.6	33.0	33.0	46.3	29.5
allo-Isoleucine	0.03	0.04	0.06	0.06	0.08	0.03	0.09	0.06	0.07	0.02	0.05	0.07	0.08	0.08	0.12	0.02	0.07	0.05	0.08	0.13	0.09	0.09	0.01	0.24	0.08	0.14	0.06	0.04	0.10	0.05
Homocystine	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00
Leucine	80.6	65.9	67.4	48.7	79.0	69.0	73.2	68.3	90.5	52.6	64.0	87.5	75.8	92.6	94.3	42.0	64.4	70.9	71.3	74.9	72.0	83.5	49.4	127.5	85.8	87.3	66.1	62.8	100.8	64.8
Phenylalanine	54.8	39.3	40.1	38.1	54.0	50.0	50.5	47.8	61.4	36.5	40.5	52.1	44.4	49.2	52.6	25.1	42.0	47.9	49.1	46.8	39.8	40.0	26.0	75.6	52.1	56.3	41.9	46.1	59.9	44.3
Tryptophan	14.3	9.4	8.5	7.9	13.8	14.5	13.1	12.9	19.1	11.3	8.5	11.8	8.2	10.9	11.7	7.8	11.9	14.6	14.0	11.8	8.7	10.0	4.7	13.6	13.0	16.4	13.9	13.3	20.9	11.0
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name
Histidine
Hydroxyproline
1-Methylhistidine
3-Methylhistidine
Asparagine
Phosphoethanolamine
Arginine
Carnosine
Taurine
Anserine
Serine
Glutamine
Ethanolamine
Glycine
Aspartic Acid
Sarcosine
Citrulline
Glutamic Acid
beta-Alanine
Threonine
Alanine
gamma-Amino-N-butyric-acid
alpha-Aminoadipic-acid
beta-Aminoisobutyric-acid
Proline
Hydroxylysine 1
Hydroxylysine 2
alpha-Amino-N-butyric-acid
Ornithine
Cystathionine 1
Cystathionine 2
Lysine
Cystine
Tyrosine
Methionine
Valine
Isoleucine
allo-Isoleucine
Homocystine
Leucine
Phenylalanine
Tryptophan
METABOLITES_END
#END