#METABOLOMICS WORKBENCH DavideS_20240227_112104 DATATRACK_ID:4677 STUDY_ID:ST003111 ANALYSIS_ID:AN005094 PROJECT_ID:PR001933
VERSION             	1
CREATED_ON             	February 29, 2024, 3:21 pm
#PROJECT
PR:PROJECT_TITLE                 	Inhibition of Asparagine Synthetase Effectively Retards Polycystic Kidney
PR:PROJECT_TITLE                 	Disease Progression.
PR:PROJECT_SUMMARY               	Polycystic Kidney Disease (PKD) is a genetic disorder characterized by bilateral
PR:PROJECT_SUMMARY               	cyst formation. We showed that PKD cells and kidneys display metabolic
PR:PROJECT_SUMMARY               	alterations, including the Warburg effect and glutaminolysis, sustained in vitro
PR:PROJECT_SUMMARY               	by the enzyme asparagine synthetase (ASNS). Here, we used antisense
PR:PROJECT_SUMMARY               	oligonucleotides (ASO) against ASNS in orthologous and slowly progressive PKD
PR:PROJECT_SUMMARY               	murine models and show that treatment leads to a drastic reduction of total
PR:PROJECT_SUMMARY               	kidney volume (measured by MRI) and a prominent rescue of renal function in the
PR:PROJECT_SUMMARY               	mouse. Mechanistically, the upregulation of an ATF4-ASNS axis in PKD is driven
PR:PROJECT_SUMMARY               	by the amino acid response (AAR) branch of the integrated stress response (ISR).
PR:PROJECT_SUMMARY               	Metabolic profiling of PKD control kidneys treated with ASNS-ASOScr-ASO revealed
PR:PROJECT_SUMMARY               	major changes in the mutants, several of which are rescued by ASNS silencing in
PR:PROJECT_SUMMARY               	vivo. Indeed, ASNS drives glutamine-dependent de novo pyrimidine synthesis and
PR:PROJECT_SUMMARY               	proliferation in cystic epithelia. Notably, while several metabolic pathways
PR:PROJECT_SUMMARY               	were completely corrected by ASNS-ASO, glycolysis was only partially restored.
PR:PROJECT_SUMMARY               	Accordingly, combining the glycolytic inhibitor 2DG with ASNS-ASO further
PR:PROJECT_SUMMARY               	improved efficacy. Our studies identify a new therapeutic target and novel
PR:PROJECT_SUMMARY               	metabolic vulnerabilities in PKD. Altogether, targeted metabolomics analysis
PR:PROJECT_SUMMARY               	performed in Tam-Cre;Pkd1ΔC/flox mouse model kidneys corroborates the central
PR:PROJECT_SUMMARY               	role of ASNS in the metabolic rewiring occurring in PKD, highlighting the
PR:PROJECT_SUMMARY               	therapeutic potential of its inhibition.
PR:INSTITUTE                     	San Raffaele University
PR:LAST_NAME                     	Stefanoni
PR:FIRST_NAME                    	Davide
PR:ADDRESS                       	Via Olgettina 58, Milan, Milan, 20132, Italy
PR:EMAIL                         	stefanoni.davide@hsr.it
PR:PHONE                         	+393337686005
#STUDY
ST:STUDY_TITLE                   	Inhibition of Asparagine Synthetase Effectively Retards Polycystic Kidney
ST:STUDY_TITLE                   	Disease Progression, investigated with targeted metabolomics in
ST:STUDY_TITLE                   	Tam-Cre;Pkd1ΔC/flox mouse model kidneys.
ST:STUDY_SUMMARY                 	Polycystic Kidney Disease (PKD) is a genetic disorder characterized by bilateral
ST:STUDY_SUMMARY                 	cyst formation. We showed that PKD cells and kidneys display metabolic
ST:STUDY_SUMMARY                 	alterations, including the Warburg effect and glutaminolysis, sustained in vitro
ST:STUDY_SUMMARY                 	by the enzyme asparagine synthetase (ASNS). Here, we used antisense
ST:STUDY_SUMMARY                 	oligonucleotides (ASO) against Asns in orthologous and slowly progressive PKD
ST:STUDY_SUMMARY                 	murine models and show that treatment leads to a drastic reduction of total
ST:STUDY_SUMMARY                 	kidney volume (measured by MRI) and a prominent rescue of renal function in the
ST:STUDY_SUMMARY                 	mouse. Mechanistically, the upregulation of an ATF4-ASNS axis in PKD is driven
ST:STUDY_SUMMARY                 	by the amino acid response (AAR) branch of the integrated stress response (ISR).
ST:STUDY_SUMMARY                 	Metabolic profiling of PKD or control kidneys treated with Asns-ASO or Scr-ASO
ST:STUDY_SUMMARY                 	revealed major changes in the mutants, several of which are rescued by Asns
ST:STUDY_SUMMARY                 	silencing in vivo. Indeed, ASNS drives glutamine-dependent de novo pyrimidine
ST:STUDY_SUMMARY                 	synthesis and proliferation in cystic epithelia. Notably, while several
ST:STUDY_SUMMARY                 	metabolic pathways were completely corrected by Asns-ASO, glycolysis was only
ST:STUDY_SUMMARY                 	partially restored. Accordingly, combining the glycolytic inhibitor 2DG with
ST:STUDY_SUMMARY                 	Asns-ASO further improved efficacy. Our studies identify a new therapeutic
ST:STUDY_SUMMARY                 	target and novel metabolic vulnerabilities in PKD. Altogether, targeted
ST:STUDY_SUMMARY                 	metabolomics analysis performed in Tam-Cre;Pkd1ΔC/flox mouse model kidneys
ST:STUDY_SUMMARY                 	corroborates the central role of ASNS in the metabolic rewiring occurring in
ST:STUDY_SUMMARY                 	PKD, highlighting the therapeutic potential of its inhibition.
ST:INSTITUTE                     	San Raffaele University
ST:LAST_NAME                     	Stefanoni
ST:FIRST_NAME                    	Davide
ST:ADDRESS                       	Via Olgettina 58, Milan, Milan, 20132, Italy
ST:EMAIL                         	stefanoni.davide@hsr.it
ST:PHONE                         	+393337686005
#SUBJECT
SU:SUBJECT_TYPE                  	Mammal
SU:SUBJECT_SPECIES               	Mus musculus
SU:TAXONOMY_ID                   	10090
#FACTORS
#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           	-	B2 - 3152	Sample source:Kidney | Factor:Ctrl-Scr-ASO	RAW_FILE_NAME(Raw file)=F3-061M-1
SUBJECT_SAMPLE_FACTORS           	-	D1 - 3442	Sample source:Kidney | Factor:Ctrl-Scr-ASO	RAW_FILE_NAME(Raw file)=F3-061M-2
SUBJECT_SAMPLE_FACTORS           	-	F4 - 3587	Sample source:Kidney | Factor:Ctrl-Scr-ASO	RAW_FILE_NAME(Raw file)=F3-061M-3
SUBJECT_SAMPLE_FACTORS           	-	G4 - 3788	Sample source:Kidney | Factor:Ctrl-Scr-ASO	RAW_FILE_NAME(Raw file)=F3-061M-4
SUBJECT_SAMPLE_FACTORS           	-	I2 - 4048	Sample source:Kidney | Factor:Ctrl-Scr-ASO	RAW_FILE_NAME(Raw file)=F3-061M-5
SUBJECT_SAMPLE_FACTORS           	-	A4 - 2931	Sample source:Kidney | Factor:Ctrl-Asns-ASO	RAW_FILE_NAME(Raw file)=F3-061M-6
SUBJECT_SAMPLE_FACTORS           	-	D3 - 3449	Sample source:Kidney | Factor:Ctrl-Asns-ASO	RAW_FILE_NAME(Raw file)=F3-061M-7
SUBJECT_SAMPLE_FACTORS           	-	F6 - 3578	Sample source:Kidney | Factor:Ctrl-Asns-ASO	RAW_FILE_NAME(Raw file)=F3-061M-8
SUBJECT_SAMPLE_FACTORS           	-	B1 - 3151	Sample source:Kidney | Factor:KO-Scr-ASO	RAW_FILE_NAME(Raw file)=F3-061M-9
SUBJECT_SAMPLE_FACTORS           	-	C1 - 3365	Sample source:Kidney | Factor:KO-Scr-ASO	RAW_FILE_NAME(Raw file)=F3-061M-10
SUBJECT_SAMPLE_FACTORS           	-	L3 - 4630	Sample source:Kidney | Factor:KO-Scr-ASO	RAW_FILE_NAME(Raw file)=F3-061M-11
SUBJECT_SAMPLE_FACTORS           	-	L4 - 4634	Sample source:Kidney | Factor:KO-Scr-ASO	RAW_FILE_NAME(Raw file)=F3-061M-12
SUBJECT_SAMPLE_FACTORS           	-	N3 - 5560	Sample source:Kidney | Factor:KO-Scr-ASO	RAW_FILE_NAME(Raw file)=F3-061M-13
SUBJECT_SAMPLE_FACTORS           	-	B4 - 3147	Sample source:Kidney | Factor:KO-Asns-ASO	RAW_FILE_NAME(Raw file)=F3-061M-14
SUBJECT_SAMPLE_FACTORS           	-	F5 - 3580	Sample source:Kidney | Factor:KO-Asns-ASO	RAW_FILE_NAME(Raw file)=F3-061M-15
SUBJECT_SAMPLE_FACTORS           	-	I4 - 4047	Sample source:Kidney | Factor:KO-Asns-ASO	RAW_FILE_NAME(Raw file)=F3-061M-16
SUBJECT_SAMPLE_FACTORS           	-	K5 - 4606	Sample source:Kidney | Factor:KO-Asns-ASO	RAW_FILE_NAME(Raw file)=F3-061M-17
SUBJECT_SAMPLE_FACTORS           	-	L6 - 4629	Sample source:Kidney | Factor:KO-Asns-ASO	RAW_FILE_NAME(Raw file)=F3-061M-18
#COLLECTION
CO:COLLECTION_SUMMARY            	Kidney tissue samples were collected and instantly frozen in liquid nitrogen.
CO:COLLECTION_SUMMARY            	Successively kidney tissue samples were grinded in dry ice and weighted.
CO:SAMPLE_TYPE                   	Kidney
#TREATMENT
TR:TREATMENT_SUMMARY             	Tam-Cre;Pkd1ΔC/flox mice and relative controls were treated with antisense
TR:TREATMENT_SUMMARY             	oligonucleotide targeting Asns (Asns-ASO). As the efficacy/tolerability was
TR:TREATMENT_SUMMARY             	dosed at 50 mg/kg/week, ASOs were administered at the same dosage via weekly
TR:TREATMENT_SUMMARY             	intraperitoneal injection for the first 2 months after Tamoxifen induction, and
TR:TREATMENT_SUMMARY             	every second week after P100 till the end of the experiment.
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	Grinded kidney tissue samples were extracted in a ratio of 15mg/1mL of ice cold
SP:SAMPLEPREP_SUMMARY            	extraction solution (methanol:acetonitrile:water 5:3:2 v/v/v). Suspensions were
SP:SAMPLEPREP_SUMMARY            	vortexed continuously for 30 min at 4°C. Insoluble material was removed by
SP:SAMPLEPREP_SUMMARY            	centrifugation at 18,000 g for 10 min at 4°C and supernatants were isolated for
SP:SAMPLEPREP_SUMMARY            	metabolomics analysis by UHPLC-MS.
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_SUMMARY        	5MM_POS_ESI
CH:CHROMATOGRAPHY_TYPE           	Reversed phase
CH:INSTRUMENT_NAME               	Thermo Vanquish
CH:COLUMN_NAME                   	Phenomenex Kinetex C18 (150 x 2.1mm,1.7um)
CH:SOLVENT_A                     	100% water; 0.1% formic acid
CH:SOLVENT_B                     	100% acetonitrile
CH:FLOW_GRADIENT                 	0-0.5 min 5% B, 0.5-1.1 min 5-95% B, 1.1-2.75 min hold at 95% B, 2.75-3 min
CH:FLOW_GRADIENT                 	95-5% B, 3-5 min hold at 5% B.
CH:FLOW_RATE                     	0.450ml/min
CH:COLUMN_TEMPERATURE            	45°C
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
AN:LABORATORY_NAME               	Angelo D'Alessandro Lab
#MS
MS:INSTRUMENT_NAME               	Thermo Q Exactive Orbitrap
MS:INSTRUMENT_TYPE               	Orbitrap
MS:MS_TYPE                       	ESI
MS:ION_MODE                      	POSITIVE
MS:MS_COMMENTS                   	The Q Exactive was run independently in positive and negative ion mode, scanning
MS:MS_COMMENTS                   	using full MS from 125-1500 m/z at 70,000 resolution and top 10 data-dependent
MS:MS_COMMENTS                   	MS2 at 17,500 resolution. Electrospray ionization was achieved with 45 Arb
MS:MS_COMMENTS                   	sheath gas, 25 Arb auxiliary gas, and 4 kV spray voltage. Calibration was
MS:MS_COMMENTS                   	performed prior to the run using the PierceTM Positive and Negative Ion
MS:MS_COMMENTS                   	Calibration Solutions (Thermo Fisher Scientific). Run order of samples was
MS:MS_COMMENTS                   	randomized and technical replicates were injected after every 4 samples to
MS:MS_COMMENTS                   	assess quality control. Metabolite assignments and correction for expected
MS:MS_COMMENTS                   	natural abundances of 13C isotopes were performed using MAVEN.
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	Peak Area
MS_METABOLITE_DATA_START
Samples	B2 - 3152	D1 - 3442	F4 - 3587	G4 - 3788	I2 - 4048	A4 - 2931	D3 - 3449	F6 - 3578	B1 - 3151	C1 - 3365	L3 - 4630	L4 - 4634	N3 - 5560	B4 - 3147	F5 - 3580	I4 - 4047	K5 - 4606	L6 - 4629
Factors	Sample source:Kidney | Factor:Ctrl-Scr-ASO	Sample source:Kidney | Factor:Ctrl-Scr-ASO	Sample source:Kidney | Factor:Ctrl-Scr-ASO	Sample source:Kidney | Factor:Ctrl-Scr-ASO	Sample source:Kidney | Factor:Ctrl-Scr-ASO	Sample source:Kidney | Factor:Ctrl-Asns-ASO	Sample source:Kidney | Factor:Ctrl-Asns-ASO	Sample source:Kidney | Factor:Ctrl-Asns-ASO	Sample source:Kidney | Factor:KO-Scr-ASO	Sample source:Kidney | Factor:KO-Scr-ASO	Sample source:Kidney | Factor:KO-Scr-ASO	Sample source:Kidney | Factor:KO-Scr-ASO	Sample source:Kidney | Factor:KO-Scr-ASO	Sample source:Kidney | Factor:KO-Asns-ASO	Sample source:Kidney | Factor:KO-Asns-ASO	Sample source:Kidney | Factor:KO-Asns-ASO	Sample source:Kidney | Factor:KO-Asns-ASO	Sample source:Kidney | Factor:KO-Asns-ASO
L-alanine	17128.16983	16712.68889	22951.72564	14134.73041	19685.73684	22964.3635	19442.00843	16576.55448	15195.27803	11793.76567	9296.091424	13593.4447	15806.43544	23721.58963	9009.562608	20977.68107	15059.34766	19205.62553
L-arginine	1871.046611	1659.924142	2358.162943	1925.511852	2033.201502	2614.452704	1649.474631	1973.185038	19775.47715	8991.594142	13909.34029	14211.25899	10882.4456	8260.253319	2963.065187	2469.15425	2951.166976	9496.499127
L-asparagine	689.6242659	690.208589	803.9415975	778.9949609	586.6129676	538.8144519	908.0528309	795.6047327	1741.675095	2102.036442	2918.944077	1357.959369	1510.894746	905.9558535	1071.720816	1109.247909	1205.353143	1061.8667
L-aspartate	9582.071877	14306.68862	8153.95122	6277.870803	9690.305148	8400.827413	8630.789051	11503.63983	2208.478311	1709.079519	6280.622556	3670.535339	3281.948459	5946.024177	5419.349134	7548.081975	10174.81924	8526.632947
L-cysteine	625.8001194	226.6568397	137.9974412	167.5608612	104.8627981	787.1767164	193.4746037	355.7815056	181.3787268	131.6771064	133.7811641	118.4751932	97.64914097	431.6014209	163.4389536	173.9565641	120.4023208	85.22144039
L-glutamate	35970.30693	40769.53482	27420.25789	37554.67907	24797.38674	44833.59533	26112.56515	32758.99179	12558.09761	19823.77922	5582.705823	13245.71319	16874.50014	32896.56706	22942.65835	49187.44778	27278.53463	20151.73451
L-glutamine	5031.336433	4115.000363	5394.1925	6926.344068	4800.243636	6537.757765	3778.062979	5814.761568	3959.547823	3053.550141	3968.657284	3523.861277	6154.379444	4197.987199	5004.547591	7446.63929	5412.129293	4090.191882
glycine	3551.011524	2113.557148	4984.576346	4856.490127	4491.85523	5028.625232	2631.636884	5435.480287	712.5680467	2429.335414	885.822323	7827.477253	1749.858295	4427.075656	3044.01128	5270.287718	2462.095665	1947.918237
L-histidine	1606.026394	1736.92712	2599.186522	1926.672342	2127.868158	2446.35891	1446.006295	2177.074211	6336.923444	7568.744086	5558.749834	4679.324107	5751.472798	5530.839411	1985.324274	2112.311215	2131.552395	4843.703057
L-leucine	35599.97033	36569.24732	38919.92829	24611.88953	23328.06873	50052.624	31203.23065	41353.04231	78128.92061	120147.2043	79769.03736	56533.15745	55758.01386	83146.2164	25991.97999	38351.24991	37792.26354	94238.24395
L-isoleucine	3759.496748	3448.746847	4156.413672	2994.352509	2553.430057	6000.340524	3449.837197	4060.402888	27584.66968	42445.76483	23643.21192	14684.90471	14529.37354	14789.73139	5883.744432	5813.073139	4366.542711	15795.77423
L-lysine	2111.952866	2004.223683	2507.292289	2374.724793	2472.446982	2663.836019	1944.676516	2289.685104	27746.79396	28602.78927	22412.7099	17163.92823	17032.66532	13452.87237	4619.861107	4459.227607	3646.138551	17184.17941
L-methionine	268.3628113	202.4504203	304.7366499	124.3773817	148.3583218	409.5528753	178.9576385	243.6409302	2507.78199	3782.911866	1529.803878	1377.08849	1952.286015	1543.37396	397.9152007	293.2660348	376.2090634	863.6661452
L-phenylalanine	1141.371029	1081.054878	1848.022999	1055.778767	776.9241057	2007.247334	1039.084927	1628.21981	13751.78145	22330.48089	11386.80605	6999.354112	9209.205153	6819.266462	2354.108879	2361.938999	2037.337182	7711.326228
L-proline	5369.378264	6014.095519	6459.795109	7035.658321	6260.945778	7845.277385	6731.635437	5375.471475	12105.16086	23385.06027	10229.83956	8876.13431	10313.06328	9885.482636	4552.060433	6054.796838	6039.517902	11195.63125
L-serine	1135.114202	1166.547669	1577.31128	1068.78429	1711.908995	1469.101322	1668.175099	1377.365222	3625.257381	2944.317534	2084.168694	3207.160876	3856.184697	3543.946563	1277.206005	1702.385325	1930.632036	2789.577027
L-threonine	3821.225891	3347.939795	4825.386444	2521.340595	3590.304952	5248.359558	4449.599365	4001.851702	12628.3646	8102.033893	7695.444093	9660.521004	11826.30403	11035.03601	4140.242052	4754.053289	5237.412693	11240.84828
L-tryptophan	6070.089801	6294.610191	9824.042977	5916.851555	4355.796063	9431.552494	5529.451924	9840.149559	36611.40754	73087.95593	40032.96576	23965.08849	27925.20336	22439.83476	12425.81701	11237.21378	11510.30132	20105.04357
L-tyrosine	1388.179459	1239.169095	2462.811088	1304.089841	1307.950064	2612.022052	1363.448269	1457.061557	13283.98919	20930.36878	11843.566	7527.706098	9678.254822	7891.725042	3234.32272	2435.294722	1976.91901	8032.032114
L-valine	109004.5998	95371.77491	111892.0137	73895.13414	92996.53236	82770.89352	138485.9948	91294.29752	38459.11172	60363.60349	41689.01055	42828.45873	52797.15743	113181.6242	88468.46602	103327.2147	136479.3672	93338.67288
L-cystine	171.3056733	29.09718353	127.7820682	10.66049997	59.2971259	317.7781349	161.7209182	306.84007	245.1088864	236.3380047	196.867188	200.6084293	764.7779834	14.30877841	29.94593533	16.87199484	4.216366373	30.20875445
ADP	1184.745045	316.5286315	920.3651379	882.9091104	865.1339738	762.3271815	985.0972722	1051.039504	564.1541234	867.1773289	697.1379926	848.9642667	431.9232975	1059.035791	576.4168049	1459.006334	476.4961895	700.6249463
AMP	77288.16471	66369.26697	72720.45041	82658.03267	72176.38463	70065.9506	69632.10586	69887.46468	8475.359713	9739.276194	16339.59772	23135.23609	10062.30816	38484.70626	37403.93296	70805.92241	35355.85934	46950.45559
Adenosine	9115.264122	3856.573652	5895.189924	7126.582078	3751.885974	8191.771655	6123.854922	6432.047919	2760.26764	2730.351227	3152.818061	1977.074593	2288.565422	4603.246971	3920.987226	5961.396519	3260.906868	3406.43487
Adenine	867.6428002	388.380835	638.2236887	484.2588746	571.5643082	710.3040549	492.4195381	375.0980816	141.7153885	130.0846144	252.1130274	145.3331565	150.4161562	286.3062092	305.964711	588.6355937	346.5415293	186.4622785
Guanosine	1974.782944	1113.828137	1018.420552	801.7300266	605.8316566	1268.528855	1385.06654	1333.587967	438.4540508	238.766362	353.7628906	423.2296968	394.5365168	573.8072326	540.3719843	909.4817818	735.0222537	775.4421217
Guanine	1016.302722	860.9142421	478.4315856	531.0079627	660.2625864	836.4172874	798.414368	688.5970699	203.0566113	390.0164022	214.4101951	211.1943945	296.1202157	468.5670084	281.6431354	511.3214151	431.0112059	727.8840576
Cytosine	92.46054359	75.59968434	90.27124056	74.90053298	34.02900889	79.36827465	70.89889542	101.0416622	216.1957747	145.0325614	251.8161158	130.4140488	140.8043476	133.9251254	101.0329909	146.0171688	101.3982542	62.1030019
Thymidine	40.1902823	123.9064906	79.55129882	188.7795926	26.73863418	68.09693057	56.90484583	61.85853146	699.3022428	1266.375062	146.4205585	164.204622	703.2161548	227.5167501	252.1932317	37.18922955	108.2752254	77.16093164
Thymine	32.73927359	44.42334554	20.93933306	43.01621778	39.65303076	38.31050727	9.619222903	40.22320328	65.82809912	62.16888597	168.9749492	107.9278051	237.5254622	120.0258354	76.23545332	73.80929589	34.89245303	90.32794606
Uracil	78.35965409	38.98968684	58.71912209	68.91712895	109.6259708	88.25912342	110.2805756	119.0234756	176.9991327	346.7592098	424.0200306	100.7832541	242.2718857	199.0396671	222.5514991	239.2235057	116.6042269	147.0077159
IDP	5.511265388	0	0	0	3.282655217	3.078461256	0	3.139983806	101.6800457	149.0271976	85.45861395	64.82233375	168.3096961	82.6721626	0	5.474481679	2.477933166	0
IMP	9704.434955	6268.391765	4422.292422	7829.129386	4466.518839	5352.47971	6784.526754	7529.965757	435.1136432	986.6957104	2354.38135	812.9397333	651.6084683	1300.732134	1842.596323	3893.645456	4085.444804	5010.876928
Hypoxanthine	17898.9265	11476.22244	10426.01849	8517.134803	5324.731279	19701.48635	9839.91491	18423.30222	3066.376856	2705.858511	3166.371564	3556.085799	4146.272774	9446.271588	3775.997386	6751.458137	12982.77189	5426.823796
Xanthine	2198.373667	1816.029182	1697.765045	1455.036438	722.0200468	3041.210801	1778.852692	2933.289053	654.2294473	638.7156084	650.8014107	883.5823222	864.4866499	1684.296984	1049.922373	1247.326192	2489.554645	979.2626854
Allantoate	54.17258043	34.6693976	34.52732046	19.0819122	71.77241932	68.07754656	67.87518771	43.47746598	335.7770804	741.8347128	424.0800427	285.7120098	371.1391248	113.7989922	68.85890068	57.20283671	76.01125584	334.8845233
5-Hydroxyisourate	373.6332857	530.4203358	827.5176456	816.8560578	643.8808093	805.8186498	290.1158782	773.028685	701.2206221	1443.700618	1246.149889	710.1029618	968.5429456	1466.771415	779.1917798	694.531736	552.0087662	586.2895144
Pyridoxal	145.8364876	120.7750549	141.5758314	100.6202123	126.8352104	59.80529301	60.10610223	46.26744981	571.6184974	689.1219395	349.2248645	486.1128262	397.3020539	473.0283648	360.1928981	52.0524799	174.5537701	105.0869512
Pyridoxamine 5'-phosphate	225.8456444	250.8308674	171.2774899	108.0960763	148.6197508	152.3835644	201.6287678	159.4352629	13.26125124	49.4601492	12.97596198	27.20949982	10.41800983	52.49565957	12.25748984	146.1583642	191.14814	163.5532172
Nicotinamide	14097.27591	5753.681554	4394.441656	4265.248509	5966.836794	8137.486226	5271.648425	5834.239967	1287.26146	1262.733674	1639.077405	1942.360637	1272.54007	2408.745005	2146.845358	4007.884975	2374.766877	3116.401629
Nicotinic acid	118.8206749	116.7805206	101.9895905	107.4451052	109.6140738	124.8805626	100.8429498	133.2206857	657.8344905	545.7756595	477.0644471	432.5467739	503.1203816	530.4694335	218.9029809	130.8441041	188.2840251	170.5248292
Cys-Gly	1542.014529	2647.031868	1498.630055	2258.376103	2271.437354	2057.009401	1922.099246	2201.53377	85.99107484	25.63280195	113.9618689	132.4089803	38.34835506	892.7583552	811.0991346	1902.777725	977.3310434	1043.386646
gamma-L-Glutamyl-L-cysteine	3629.200497	1806.412417	1024.226191	1636.00657	799.9524365	3754.117685	1189.643844	2065.308818	95.77243729	93.04945581	101.8696902	190.7941268	96.74018396	794.0474551	486.2658578	1092.693828	642.1203076	582.6766922
gamma-Glutamyl-Se-methylselenocysteine	21.79143964	8.650776071	4.086515189	15.8364679	22.53977718	25.60899277	10.91925609	14.11445372	152.1718706	418.3831843	153.76442	120.0607286	177.1440859	42.57276835	40.62842467	45.67988478	29.45958799	154.3736135
gamma-L-Glutamyl-D-alanine	963.1921938	662.200101	406.6709067	471.5320978	398.7459075	1205.899248	514.2660595	469.5000925	375.4459456	470.4335855	372.5635944	408.3372939	398.6339393	417.0914696	260.8804561	436.3323945	116.8791495	321.4442633
(5-L-Glutamyl)-L-glutamine	1302.157816	601.4022829	384.1815025	394.0802274	287.4303002	1444.148236	510.2675974	917.6617062	365.3533805	456.3811989	454.4341262	497.0535692	295.5843368	390.4459807	218.202606	163.7955173	120.6904539	349.503127
L-Homocysteine	17898.9265	11476.22244	10426.01849	8517.134803	5324.731279	19701.48635	9839.91491	18423.30222	3066.376856	2705.858511	3166.371564	3556.085799	4146.272774	9446.271588	3775.997386	6751.458137	12982.77189	5426.823796
Dimethylglycine	1243.353491	1117.649975	1234.065362	1389.285113	702.6447091	1424.697913	1093.396116	1028.526763	1422.768439	878.5220755	1472.13645	1885.805239	1818.237938	2264.706512	1525.858212	867.2294872	1134.330552	1055.41621
S-Adenosyl-L-homocysteine	1859.72482	1764.826066	2219.731784	2870.946508	2813.10947	3217.563203	1801.721997	2520.602217	293.3522426	187.0991775	308.249619	240.2324052	256.7673478	1356.505733	1055.883721	2210.613648	1362.065883	1193.834615
S-Adenosyl-L-methionine	65.28721841	106.3179505	200.6581646	207.0468535	219.3934473	160.4137728	128.0001383	141.1964404	217.3935787	104.0473816	181.0652669	155.6600996	133.6359116	246.6673862	210.3993945	164.2571628	124.9118448	160.3609769
Ornithine	182.2358316	180.611018	272.3772141	182.7368827	326.3797891	290.3898049	240.4048209	250.7481028	1325.55253	3185.564284	2047.687223	1263.828233	1382.019935	734.1405363	371.0807177	290.3589435	373.1253481	1636.475867
L-Citrulline	539.9830288	733.3375027	645.4745064	616.1587427	752.5576407	567.5224776	1020.205922	567.9689475	7142.459112	2660.492277	6831.889023	7968.636201	8258.070068	2534.246264	1124.208911	757.234033	1319.07164	2471.239307
5-Methylthioadenosine	5735.599589	4857.71183	13678.54305	15760.01584	16127.40658	10057.13569	5767.258013	8437.754734	9675.864978	9468.61421	10966.89102	9274.491007	8745.715634	11439.16583	10967.46361	11198.34502	6401.551261	6684.414969
Putrescine	54.75425374	71.67639196	222.5354422	166.1347337	294.2780841	89.15371626	98.81863437	111.5368018	259.9703003	146.6972907	151.646972	210.3454508	221.3379695	212.7694722	178.6372922	145.8874982	128.8701233	161.0301078
Spermidine	347.3946059	286.7731568	412.2411314	964.7348804	2076.023584	379.6572492	1056.074501	911.9457189	4641.374807	3867.767918	5103.711488	7214.223306	4731.445413	1391.78463	4865.726863	2650.753088	1895.268972	3893.162245
Spermine	84.15530712	103.882439	75.38271658	112.4857511	93.96140969	132.9704789	162.3037138	99.98094803	495.4810414	1151.630016	1229.219615	726.8564846	768.0550287	865.231914	1571.311164	235.7659214	142.7396371	675.6667589
N1-Acetylspermidine	1151.83138	903.2893559	1170.538479	1647.750474	1375.61556	970.4710169	1629.243846	801.0374309	5456.098752	4433.687899	3261.114736	2887.533864	3933.521794	4132.290782	3704.657855	2115.609047	2021.851654	1725.160261
alpha-D-Glucosamine 1-phosphate	17.80631685	34.11204356	48.26946091	38.60144391	11.75705721	14.38746219	14.04975958	32.86649343	95.36704368	82.07215099	120.5192115	73.95910137	94.78410786	170.6017276	65.65476218	18.23324966	39.11190649	40.83140841
N-acetyl-D-glucosamine	74.30441729	98.2425212	96.59643622	119.3744964	38.56558349	101.1555425	112.6774742	113.7946308	343.7682658	379.0438473	509.2193306	443.7257362	417.1662001	660.1961515	306.9034506	128.7239781	185.5386372	234.8714513
Asymmetric dimethyl arginine	677.4924266	734.8294338	827.8934659	1069.166741	854.4328528	801.6898558	949.2946242	858.7368681	8439.027447	4885.976776	11463.42645	8865.623586	5802.716722	11757.13882	5529.003031	1451.011706	3528.342435	5018.215254
Carnosine	639.550141	614.7268765	204.8588835	304.5309499	243.3550161	334.3063187	744.1224085	302.8581864	132.1822384	99.85801261	130.188746	125.5158735	265.6996779	284.2659882	181.1280099	421.7695198	484.021266	501.0326472
Creatine	44225.61223	38258.37245	61624.27825	29351.3436	32114.87846	32006.07296	36670.465	36360.76719	43724.56109	27050.98454	20939.4104	54061.84927	53278.44198	44144.95179	17874.27566	26457.31099	56237.75534	28321.47883
Creatinine	2292.805674	4036.57841	5492.007629	4489.970391	3211.410055	1773.254284	3080.224946	2931.334074	31989.96638	9380.345552	20839.67202	44512.20225	28384.10703	40334.04278	17904.85648	4259.480491	8190.157171	7960.729565
4-Acetamidobutanoate	65.8723987	42.21806648	164.4553388	121.4407681	232.6137243	0	63.17529232	54.94138595	795.4814892	634.6248172	1105.387421	1400.169489	935.2594537	535.3470624	399.9998744	199.0862745	277.1780721	509.1643667
Guanidinoacetate	29175.75253	27511.75009	13963.59001	12643.47265	20476.08157	13888.79579	33057.55345	10741.70876	1604.784287	1329.727744	2858.448923	2792.919494	2294.801462	18183.70566	9917.99166	12849.08598	23634.09378	18804.72086
trans-4-Hydroxy-L-proline	546.0572377	547.380834	1114.482347	605.7267024	684.7907612	618.8033847	839.349798	767.9025072	498.3514051	460.9685778	558.246719	582.4394931	1085.92307	1080.385492	638.6473818	633.6521735	534.2420463	820.7883337
Pantothenol	569.1627219	353.4879437	506.0727447	417.3609329	384.2496016	542.797536	443.1533978	396.54595	2387.226204	2769.997903	1023.686499	1460.092859	1811.190831	1072.707001	714.2600667	554.5174651	477.0409822	823.5390777
5-6-Dihydrouracil	417.3432067	611.6333416	544.3588414	583.1148728	358.4395379	226.2634208	522.6073048	240.2450303	388.7255224	301.4919963	866.3813093	616.2773422	223.7891541	788.828183	906.2065218	306.5980249	1173.84001	615.116087
Pantetheine	51.22964145	33.47470498	26.95967565	42.57438793	28.91056143	39.99155794	22.61249272	21.24134186	1957.179202	4570.207437	1473.441045	1356.214973	2724.92753	1671.200025	396.7834041	23.79823298	136.7600528	147.9771454
Pantetheine 4--phosphate	60.44105026	45.76824781	191.4517803	284.1378242	141.0198164	619.583336	75.94013438	530.52529	586.8682291	459.2858672	404.7251093	342.7342819	317.0253467	280.9825666	184.2405462	125.5069084	50.12193458	61.81180579
D-4--Phosphopantothenate	4.408009188	4.037392028	31.84579781	38.79171327	32.34210496	112.1063983	6.664566764	80.40930904	3.700033748	3.293563823	12.27280448	3.318343474	3.304102603	54.4504349	15.50767939	22.23845785	5.13401048	4.487345898
L-Methionine S-oxide	109.4592823	140.355914	64.38972602	40.18343413	37.74940192	116.8989927	102.6301555	41.96395742	1587.033891	583.2250556	862.8831332	1653.203502	1582.0017	1397.970934	451.075464	56.83938654	532.7538135	630.5815934
5-Hydroxyindoleacetate	82.48288795	125.9907307	110.8969254	109.7727804	1392.948946	150.9111448	57.76701341	77.16595618	576.1187757	1182.101296	532.5884118	474.0105729	547.8383986	232.278585	158.5590292	499.2880864	48.69632996	45.35939824
Indole	9.596430072	6.075132194	14.81232907	16.90187427	8.782018568	3.341735637	10.22077626	7.782779258	346.4052562	53.34610748	258.3229146	322.629876	414.7270031	69.88178976	64.69981916	8.304697537	21.34225348	29.80529925
Indole-3-acetate	6848.059368	1794.6022	1851.898526	3690.119848	2581.005086	8134.397537	2976.394244	5255.26001	927.765111	835.6035831	894.6901247	911.2245572	632.42639	1548.542604	887.7303727	3141.821461	1103.990497	1571.595547
Indoxyl	34.23232644	44.74412172	62.59710048	97.56452722	115.9171288	145.6934031	34.59939837	37.20820548	816.8652397	657.8631839	800.530386	542.0252362	857.660673	815.599668	385.9423867	56.32156568	112.2420481	112.9418874
Kynurenine	3.769128815	6.598378023	6.214781229	9.511171037	3.51690842	4.98889949	5.929665405	11.19565421	23.75965625	29.18767624	33.15933225	14.67787801	28.8553425	18.63873253	6.367902151	9.545902846	8.617739088	14.75420254
Kynurenic acid	384.1396738	331.813433	703.400813	864.1460269	728.6100999	100.2719505	299.6308763	116.2379087	11284.31055	10379.92536	6521.502572	7248.13002	6899.126031	4591.97619	2473.968371	750.2162564	1703.928394	1536.673724
Anthranilate	1412.512767	757.9041841	986.573135	1177.270852	868.1773908	1515.290101	1364.533518	1579.07752	6187.90632	4864.982109	4590.96108	6582.827457	5445.797171	3584.100793	1834.460569	890.3882774	1243.673709	1800.777027
L-Adrenaline	460.7710394	588.8202754	510.8102221	1099.84997	720.2179715	443.6508782	672.9633273	575.1392456	441.7791736	323.6471539	392.5105053	399.7244174	477.6254356	397.1791184	698.9417257	1155.340268	738.0196336	687.5006967
Diethanolamine	2369.261563	391.0618056	442.2276839	622.4290871	336.1075012	430.4178486	369.9204827	353.419207	690.4113587	3053.769599	258.5307826	490.8056694	491.5443021	341.6713496	1784.213901	1279.45302	606.2593801	681.2585356
Triethanolamine	993.0760876	285.0093395	376.8580452	546.0465255	571.6357134	273.2114917	363.2537862	494.4526687	370.7956962	1951.718523	269.0630586	483.2966612	506.7682736	387.3449218	1007.878584	873.0566775	485.8091859	807.037547
CDP-choline	652.3396339	704.9989736	700.3158224	384.6280998	529.2159767	584.6907162	686.9416211	501.0881212	200.8743218	76.86493017	201.9427378	488.7810606	312.8474551	621.058051	396.5291165	440.8260415	738.6630042	666.7941112
Sphingosine	3980.025562	2005.678759	8818.127661	5785.440724	6555.274108	6569.83762	6745.530711	11824.31334	7064.196174	7011.081438	5473.772632	5474.806871	5990.574554	10832.99342	10009.77749	11562.9085	9327.766426	9958.55525
Choline	118212.7184	53157.55973	51783.01667	36059.6264	45858.21767	98818.34106	77072.59412	69000.72276	39208.02313	52373.75711	38014.13393	36495.9324	48178.34332	58792.65706	44233.22555	58411.8888	36711.56675	43232.06697
L-Carnitine	161643.5097	141035.7572	138537.7705	184240.4187	127143.9135	108852.7158	113728.9037	109790.7106	45560.43082	45111.51247	35467.1006	50450.57006	50097.8576	96814.26403	70241.50341	149290.6671	109024.5704	102217.4674
Propenoylcarnitine	185.5513899	161.3920277	675.1775677	1153.705508	430.9478482	364.9793457	193.3641659	664.7012758	2637.357717	1881.660632	2581.553449	1868.632537	1324.82818	4219.418079	2883.088294	880.4845789	334.3156281	274.989592
Malonylcarnitine	406.6538182	443.5641603	462.4773424	520.4346379	301.4377976	444.61434	308.6911154	336.4187931	253.1957166	274.525651	249.9003074	215.1974469	199.8261825	263.9743736	216.3840799	318.9411755	138.4469717	162.0379488
Propanoyl-carnitine	33067.80657	12939.64246	16845.07402	44245.07275	21463.59483	13401.82356	16267.34127	21151.46127	4121.193437	5974.103247	4952.460103	3550.70036	4140.555767	10428.92609	10871.97951	23794.39444	8941.21102	14230.59199
Hydroxypropionylcarnitine	76.15147109	93.49380872	62.60639715	98.50069836	88.20293059	48.8253484	62.85096724	65.75286822	194.8740782	378.5026253	105.8957872	102.3825758	98.00879086	81.14030299	89.00077387	75.10635417	68.20361914	67.29592464
Methylmalonylcarnitine	588.400076	747.6175239	574.2302376	569.4696779	541.2247531	310.3424544	468.369061	404.5085695	633.2880857	527.2057784	724.0904375	435.8947239	318.2743401	554.7769813	314.2483323	491.884415	306.8621321	519.2962099
Butyrylcarnitine	6149.548937	6064.280975	8464.425601	7300.785661	2502.568712	6540.208141	3459.720491	6832.01655	5675.440296	5298.625355	5863.4078	4089.967328	5131.434447	7724.576219	4141.22273	4141.996815	3027.858789	3725.148793
isobutyrylcarnitine	733.3915739	751.6874007	904.9103437	895.8122293	245.3284868	705.0580183	390.353269	726.1669495	637.2202341	529.224521	641.6891409	413.0861212	605.1798693	644.454933	471.9818833	510.8807442	386.4209932	404.2794046
Tiglylcarnitine	103.0099418	83.97359479	175.5311323	222.1847447	322.4600109	159.2938362	52.46396927	164.202454	946.262302	1170.203468	1189.238437	895.2213996	661.9602238	1154.458423	400.69196	152.8079721	125.5417741	92.08740957
Isovalerylcarnitine	2381.907079	1569.273292	2382.228446	3257.26344	1045.075096	1566.155272	940.1661586	1148.330526	3241.990881	5525.159386	2624.636961	1912.079499	2447.682634	2044.400868	2063.624195	1449.714762	1384.411055	1116.831
Hydroxyisovaleroyl carnitine	6431.831124	3416.248024	3160.264326	7659.466351	5181.950196	2746.522847	2085.334285	3429.560503	1190.264387	1829.429653	1120.294617	761.9184594	1451.743707	1902.470386	1307.584064	4292.009919	1644.077715	3156.330137
Methylglutarylcarnitine	2384.211481	1893.873833	1266.518274	3061.422457	1886.885388	2175.844857	1687.462188	1859.357544	596.1180999	342.1048117	931.5776396	595.9738676	346.0587671	767.5171225	753.9701229	1360.149161	432.6726425	1438.785752
Hexanoylcarnitine	2359.961065	1945.384288	5798.639704	7459.956434	1386.10333	3797.813323	1819.06686	5019.686908	2818.117431	1862.448783	4759.213006	1793.181556	2050.93277	7637.2232	5322.980342	3837.417915	1535.684119	2058.459376
Pimelylcarnitine	77.47140736	66.6578209	63.27485216	63.1416126	45.55428405	50.6356746	41.98697593	21.38415865	115.1331604	124.4978942	138.2473929	104.1062223	116.0867516	78.97235457	109.0577145	82.63971989	57.75623743	44.40068044
Hydroxyhexanoyl carnitine	88.68513333	17.06361598	39.21938573	60.40779138	35.11312563	47.6892414	34.71413385	34.75818146	156.4862155	335.4563515	315.774568	116.9340241	359.3118184	75.68914971	73.17594913	16.20986514	42.16335766	65.22461571
Octenoylcarnitine	148.2348762	226.2815296	171.3255674	280.9986349	96.27981373	121.9927405	105.1055828	165.459354	184.1762729	124.6414379	217.0005424	127.6646164	138.7149046	214.525638	227.5039974	109.4195451	62.05569999	106.025048
Octanoylcarnitine	1432.22452	1026.296581	3089.133938	4721.174438	1804.314608	2859.985616	1229.072959	4081.724023	1573.653823	1176.267602	2173.030349	921.0799232	1123.759508	3607.598804	2789.958331	2883.649411	781.9942995	1487.294235
Hydroxyoctanoyl carnitine	348.7518691	202.649489	471.0259456	570.7617752	190.8483255	477.5500675	290.0782579	535.5406474	400.5618831	295.5798734	688.5358283	307.1838811	350.4120075	694.2210818	580.580286	616.2195727	248.5793892	570.6004543
Nonanoylcarnitine	192.7687452	43.75113758	103.9936675	252.0048753	94.9119658	129.1115307	258.2846567	131.4999723	74.16959641	373.5158339	48.57433823	45.7164721	58.36932049	102.9398023	121.8312028	78.35831506	26.26517975	68.14287833
Decanoylcarnitine	1208.341379	668.0545819	1816.402834	3602.933889	985.9559073	2486.601134	1309.49951	3985.856068	1254.101541	1113.77228	1348.838847	663.1580791	889.9318605	2748.08632	2060.123596	2251.734529	610.278884	1273.789063
Dodecenoylcarnitine	5730.747211	6499.129345	5820.405906	5675.117654	5721.016948	5965.247815	5918.603767	5734.366409	4576.828607	3691.884813	5714.513103	5729.19904	5810.015057	5857.026381	5388.428155	4919.634813	5784.9625	5515.707131
Dodecanedioylcarnitine	1809.526612	1657.152994	265.7049065	902.2417267	202.6471935	204.8930605	1297.449542	223.5214762	4247.371861	1488.195847	4379.032644	3601.494116	1926.325471	1192.172054	1201.636169	461.847107	1002.59861	1804.050629
Dodecanoylcarnitine	4835.517139	1753.388225	2374.417455	7345.246457	2216.626517	4247.166543	3489.815441	5339.378959	1980.267853	2451.57984	2916.186491	1222.593216	1956.915223	3715.435109	3246.213279	4044.467192	1169.323536	2346.736579
Hydroxydodecanoyl carnitine	426.3159627	109.3994979	372.9492342	847.3536085	134.8828645	796.1640104	441.1254734	964.1281099	425.4074647	290.4380099	542.5994875	285.6752822	239.6321386	664.0373735	460.3137298	632.0968618	272.7930776	579.4085737
Tetradecenoylcarnitine	4976.329215	1494.783859	2227.9075	7638.824932	1697.846661	2804.960534	3153.29501	4860.803069	3000.749232	2570.014863	3383.885656	1497.185181	2033.929678	3600.582303	3430.865098	3557.705384	763.4941754	2455.920838
Hydroxytetradecenoylcarnitine	455.8722411	155.3919116	432.4242211	877.7085847	143.1664679	674.6139012	397.6690748	987.1781201	459.7680445	373.2755742	808.7358157	351.057291	260.8904032	653.029169	528.3698392	552.8912488	183.628037	525.9657119
Tetradecanoylcarnitine	22455.12517	7031.455052	7319.53969	23938.18043	8816.658558	14493.80643	10902.49912	16969.05517	6850.222215	8410.46664	8908.000601	4529.578808	8219.189826	12374.84217	10012.46575	12764.90582	4513.079446	9661.365229
Hydroxytetradecanoyl carnitine	884.6336496	322.8204004	705.8199884	1752.842412	298.9710548	2061.545515	1192.145146	2443.72294	562.0913842	511.5362298	742.5116228	388.4885784	353.1837933	1330.852527	895.5390678	1998.215915	750.2010808	1189.679806
Pentadecanoylcarnitine	673.4439742	284.069215	226.805663	978.8340692	413.1858468	427.6983486	464.1881087	586.9475506	375.924042	600.9309454	503.1075014	332.1610699	877.7597228	592.4118008	426.6532699	494.3343242	168.7965918	302.7189276
Hydroxypentadecanoyl carnitine	800.167956	1890.889716	571.1880958	311.0747109	170.2213165	604.828279	472.275194	170.1002939	442.5504531	327.8172665	769.2296742	214.2172792	309.7127292	414.4748834	727.3762821	792.9795492	238.1862445	371.0883693
Hexadecadienoylcarnitine	4044.400878	2063.454585	1609.790973	6096.565552	2273.482877	3005.378439	2982.157161	5867.567711	2491.291554	3528.096309	2824.653158	1473.654014	3456.457091	4563.55056	4082.713628	4248.189305	1326.895383	2707.42326
Hexadecenoyl carnitine	12287.51975	5157.629641	10274.21364	28916.88673	6505.949455	8665.358712	10200.18203	15096.96794	5838.79776	6116.897083	11435.24822	4524.820799	5684.115915	13453.70129	9954.693751	11300.88388	3482.420187	5734.534744
Hydroxyhexadecenoylcarnitine	931.3455416	243.7330043	696.6291623	1699.689418	233.6845633	1519.831315	932.1603076	1938.074476	545.3962685	430.1111477	812.6149131	372.322187	406.2912607	1166.773008	896.8991366	1496.369012	430.3514074	899.2363126
Palmitoylcarnitine	43847.1777	14326.21127	15057.57504	48958.52419	22647.30742	26993.32986	29664.75242	35491.5474	15944.31696	20994.0172	20774.63357	14522.95896	26812.727	36466.39729	19310.80929	34752.63406	16640.31767	22235.20593
Hydroxyhexadecanoyl carnitine	2718.214542	902.2917171	1679.190828	4338.294343	1141.321804	5141.540913	2828.540162	6911.251239	1092.440943	1106.673142	1912.814051	897.0673439	1025.885181	3071.217758	2250.382749	5051.411645	1517.33945	2749.142239
Heptadecanoyl carnitine	142.4349766	72.84282472	68.89006813	132.1768823	56.8406618	107.606324	125.1390968	179.1466326	133.5614361	166.3339299	118.9379864	86.78700522	154.4844339	177.6771461	153.1705296	123.3732518	66.90658661	82.78272797
Alpha-linolenyl carnitine	2224.13527	1239.090029	1250.110221	5209.430855	1510.362482	1644.731925	1988.055889	3502.189326	932.7864622	1758.591301	1504.352164	569.2482921	1921.6325	1889.430814	1781.785799	1770.854237	745.3733147	1366.301034
Linoleyl carnitine	27673.72134	15956.44472	13217.12711	65354.76913	20488.36236	20584.0199	25149.65551	35103.42087	15261.3877	27657.7678	18230.15077	12342.20434	32964.86728	29670.36358	22871.26924	27893.52581	10734.97792	19406.17352
Octadecenylcarnitine	12538.69061	5479.025444	8648.293132	27564.29096	8500.484959	8808.797832	13683.84815	18138.22975	7740.897045	8011.704409	7520.959952	7152.605111	10333.2405	14639.36504	9487.806929	13764.20252	5150.090281	11634.92902
Hydroxyoctadecenoylcarnitine	2009.077337	693.4537555	1433.744634	2929.157198	616.4427439	2989.614904	2239.068609	4561.950104	1231.870888	820.8594934	1791.68057	978.7910929	840.8506559	2595.170716	1792.185575	3566.133602	1158.207699	1907.603323
Stearoylcarnitine	3197.982803	1543.566525	847.4095926	1931.846087	842.5554286	2792.127555	1690.969164	2277.899116	2293.229062	2079.919515	2503.540463	1600.415233	2584.205998	2983.07025	2561.545836	2849.17648	1702.19021	2155.45849
Arachidyl carnitine	72.05629304	48.19042007	27.94243218	57.98264776	25.56312153	88.39274085	46.78690301	80.96179157	142.1035355	132.9595116	113.9013831	110.3574378	165.5492601	157.9405263	139.2498778	115.7477993	60.54166858	87.98169783
Docosapentaenoyl carnitine	379.8853939	243.0374754	375.7602981	458.5302734	562.6786432	330.3698344	430.2075576	454.7562578	301.4189237	368.4365858	288.5115964	462.7394091	410.9922656	361.1657968	251.3224816	445.2751817	368.4339077	502.2554977
Acetylcarnitine	241504.2258	194385.3971	160779.5185	197702.4857	158175.5574	131784.6111	89356.38118	165980.2992	83027.14502	117334.2784	126144.6806	82324.39816	86748.97685	134168.9718	100516.1635	162247.8572	81392.76696	177497.3339
Mevalonate	5.394008709	9.190304468	27.36778556	33.04982535	12.927706	7.287682326	12.72935147	5.181589297	55.09339739	16.21877923	42.17993609	43.17211682	43.35850937	37.8053605	21.64217002	4.642502141	10.84576519	10.42274106
Cholesterol	264.0985842	152.7898634	208.3116602	241.8498223	238.0652219	316.3699887	230.8663579	227.2034178	327.2694131	236.4873381	233.0646576	275.4775079	198.0186236	258.4588577	206.5591927	204.0657969	254.9614468	174.8344557
Riboflavin	160.9970785	137.4004902	306.0912351	355.7558728	186.3556987	348.4484839	173.1309583	292.7359077	1827.135454	4214.213727	1005.255622	1666.648608	1043.919707	670.3528623	619.7784514	270.54415	271.7666178	270.6006441
N-Acetyl-leucyl-leucine	9.121857236	7.346543401	11.85938437	4.138024368	4.787498357	5.616495053	4.449664404	5.271571909	484.5206593	451.8213657	688.3919785	470.5191557	441.718471	216.3177662	75.17833006	20.18441599	37.82320144	39.6282608
N6-Methyl-L-lysine	138.7819835	508.0626663	145.1209371	133.4223049	259.2316676	398.6640356	794.9606715	120.6584193	1691.72157	752.3047559	1149.157152	1043.445181	1234.8661	322.7779341	156.4739729	124.211674	461.5191092	305.3299026
N-Amidino-L-aspartate	67.42408865	3.188380067	314.1863545	198.3314458	203.2380232	98.15821352	5.373798329	79.20034623	1468.667733	220.9042523	1216.804029	1979.129043	742.8030206	647.1266106	293.0696442	67.87822283	116.4277189	177.4523171
N-Acyl-D-glutamate	3.531923376	9.959629022	16.4799405	12.21465246	2.349167232	6.107105607	2.946298019	3.225610117	60.21405331	51.30495853	43.43594339	45.64364178	56.7459097	59.26806264	83.24762538	10.28358811	27.04025957	22.89569055
N-Carbamyl-L-glutamate	60.15092775	65.10100439	153.9066119	186.8318822	144.1783897	106.7137797	37.70775181	30.15320396	1353.491009	637.0688603	906.3932204	1795.607107	1022.362648	774.4800627	446.0875247	73.0505907	260.6952878	227.351986
N4-(Acetyl-beta-D-glucosaminyl)asparagine	21.92428387	8.485009634	8.804154596	22.78516343	11.32407837	13.14114689	5.677724293	9.221457887	181.0591457	230.0466184	310.0490162	230.7589807	247.2114138	118.2902034	17.65184415	5.758810665	27.19881311	17.8029374
N-Acetyl-L-aspartate	44.48955357	38.40073014	44.64153951	50.25088926	27.45545995	34.52973071	48.59094216	46.09721485	271.8660884	356.0391089	244.7474766	214.6296995	198.7357044	370.7668753	285.707929	78.46541171	54.71739862	52.96953484
N6-N6-N6-Trimethyl-L-lysine	2654.05347	2529.401537	3913.734801	2643.246885	2421.061503	2405.041639	2141.935593	2042.333666	13479.48713	9770.303362	17034.41244	11995.58892	12164.19027	13409.0033	7152.880568	2930.801013	4383.243565	6624.936667
N-Carbamoyl-L-aspartate	8.54762636	4.413980603	7.901973476	5.531207202	4.72611658	1.512811055	6.914650392	1.794741179	10.1439798	49.28278734	63.50061659	18.76189475	31.04655839	28.48359622	22.74961547	28.42607163	9.579906012	20.63815534
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	KEGG ID	m/z	r.t.
L-alanine	C00041	90.0551	0.6590533
L-arginine	C00062	175.1189	0.6261634
L-asparagine	C00152	133.0606	0.6725533
L-aspartate	C00049	134.0449	0.6533499
L-cysteine	C00097	122.0269	0.9994332
L-glutamate	C00025	148.0605	0.6568276
L-glutamine	C00064	147.0764	0.6522999
glycine	C00037	76.03932	0.6841066
L-histidine	C00135	156.0768	0.6054105
L-leucine	C00123	132.102	0.7009134
L-isoleucine	C00407	132.102	0.9453866
L-lysine	C00047	147.1128	0.5982434
L-methionine	C00073	150.0571	0.8750101
L-phenylalanine	C00079	166.0863	1.41141
L-proline	C00148	116.0708	0.6854568
L-serine	C00065	106.05	0.6612967
L-threonine	C00188	120.0657	0.6554534
L-tryptophan	C00078	205.0971	1.76741
L-tyrosine	C00082	182.0811	0.9105799
L-valine	C00183	118.0864	0.6746566
L-cystine	C00491	241.0275	0.9605599
ADP	C00008	428.0369	0.8469286
AMP	C00020	348.0703	0.6868101
Adenosine	C00212	268.1039	0.8966232
Adenine	C00147	136.0618	0.6899601
Guanosine	C00387	284.099	0.6862751
Guanine	C00242	152.0562	0.6857035
Cytosine	C00380	112.0507	0.6644499
Thymidine	C00214	243.1002	1.833355
Thymine	C00178	127.0503	0.6685035
Uracil	C00106	113.0347	0.6937134
IDP	C00104	429.0277	0.7686882
IMP	C00130	349.0545	0.6889149
Hypoxanthine	C00262	137.0459	0.6943898
Xanthine	C00385	153.0405	0.6854846
Allantoate	C00499	177.0624	0.6150534
5-Hydroxyisourate	C11821	185.032	0.6499479
Pyridoxal	C00250	168.0651	0.6796483
Pyridoxamine 5'-phosphate	C00647	249.0632	0.6515625
Nicotinamide	C00153	123.0554	0.6939243
Nicotinic acid	C00253	124.0401	0.5626667
Cys-Gly	C01419	179.0475	0.6858621
gamma-L-Glutamyl-L-cysteine	C00669	251.0697	0.6878858
gamma-Glutamyl-Se-methylselenocysteine	C05695	313.0359	0.6258542
gamma-L-Glutamyl-D-alanine	C03738	219.0983	0.6925101
(5-L-Glutamyl)-L-glutamine	C05283	276.1188	0.6670761
L-Homocysteine	C00155	137.0458	0.6858516
Dimethylglycine	C01026	104.0708	0.6698599
S-Adenosyl-L-homocysteine	C00021	385.1289	0.683976
S-Adenosyl-L-methionine	C00019	399.1445	0.63176
Ornithine	C01602	133.0973	0.6048468
L-Citrulline	C00327	176.1031	0.6553033
5-Methylthioadenosine	C00170	298.0966	1.754876
Putrescine	C00134	89.1075	0.6057242
Spermidine	C00315	146.1652	0.6070967
Spermine	C00750	203.223	0.6055621
N1-Acetylspermidine	C00612	188.1757	0.6153567
alpha-D-Glucosamine 1-phosphate	C06156	260.053	0.690025
N-acetyl-D-glucosamine	C00140	222.0972	0.682188
Asymmetric dimethyl arginine	C03626	203.1502	0.6507333
Carnosine	C00386	227.1142	0.60166
Creatine	C00300	132.0768	0.6644533
Creatinine	C00791	114.0664	0.6746666
4-Acetamidobutanoate	C02946	146.0812	0.6005074
Guanidinoacetate	C00581	118.0613	0.6519999
trans-4-Hydroxy-L-proline	C01157	132.0656	0.6554449
Pantothenol	C00864	220.118	1.6805
5-6-Dihydrouracil	C00429	115.0503	0.8289334
Pantetheine	C00831	279.1355	1.792187
Pantetheine 4--phosphate	C01134	359.1016	1.73902
D-4--Phosphopantothenate	C03492	300.0822	1.042483
L-Methionine S-oxide	C02989	166.0521	0.67046
5-Hydroxyindoleacetate	C05635	192.0665	1.83403
Indole	C00463	118.0651	1.946164
Indole-3-acetate	C00954	176.0733	1.730793
Indoxyl	C05658	134.0601	1.808973
Kynurenine	C00328	209.0918	1.374193
Kynurenic acid	C01717	190.0502	1.793284
Anthranilate	C00108	138.0549	0.67616
L-Adrenaline	C00788	184.096	0.6650432
Diethanolamine	C06772	106.0864	0.6390767
Triethanolamine	C06771	150.1125	0.6435801
CDP-choline	C00307	489.1131	0.6545792
Sphingosine	C00319	300.2897	2.080372
Choline	C00114	104.1072	0.6455266
L-Carnitine	C00318	162.1125	0.6534999
Propenoylcarnitine	HMDB0013124	216.123	1.855946
Malonylcarnitine	HMDB0062592	248.1129	0.6874081
Propanoyl-carnitine	HMDB0062514	218.1387	0.6964101
Hydroxypropionylcarnitine	HMDB0013125	234.1337	1.819624
Methylmalonylcarnitine	HMDB0013133	262.1314	0.695618
Butyrylcarnitine	HMDB0002013	232.1542	0.6930593
isobutyrylcarnitine	HMDB0062556	233.1577	0.6856081
Tiglylcarnitine	HMDB02366	244.1543	1.877546
Isovalerylcarnitine	HMDB0000688	246.17	1.794713
Hydroxyisovaleroyl carnitine	HMDB0062555	262.1649	0.6884795
Methylglutarylcarnitine	HMDB0000552	290.1597	0.6842847
Hexanoylcarnitine	HMDB0000705	260.1855	1.829377
Pimelylcarnitine	HMDB0013328	304.1754	1.839262
Hydroxyhexanoyl carnitine	HMDB0061633	290.1953	1.805677
Octenoylcarnitine	HMDB0013324	286.2011	1.856386
Octanoylcarnitine	HMDB0000791	288.2169	1.877257
Hydroxyoctanoyl carnitine	HMDB0061634	304.2119	1.81377
Nonanoylcarnitine	HMDB0013288	302.2325	1.937083
Decanoylcarnitine	HMDB0000651	316.2481	1.936611
Dodecenoylcarnitine	HMDB0013326	342.2638	1.848283
Dodecanedioylcarnitine	HMDB0013327	374.2536	1.844177
Dodecanoylcarnitine	HMDB0002250	344.2798	2.009796
Hydroxydodecanoyl carnitine	HMDB0061638	360.2744	1.920497
Tetradecenoylcarnitine	HMDB0062588	370.2945	2.036315
Hydroxytetradecenoylcarnitine	HMDB0013330	386.2899	1.961042
Tetradecanoylcarnitine	HMDB0005066	372.3112	2.089033
Hydroxytetradecanoyl carnitine	HMDB0061640	388.3055	1.989812
Pentadecanoylcarnitine	HMDB0062517	386.3264	2.157203
Hydroxypentadecanoyl carnitine	HMDB0061641	402.3133	2.395159
Hexadecadienoylcarnitine	HMDB0013334	396.3109	2.05958
Hexadecenoyl carnitine	HMDB0006317	398.3266	2.112303
Hydroxyhexadecenoylcarnitine	HMDB0013333	414.3213	2.018566
Palmitoylcarnitine	HMDB0000222	400.3423	2.25592
Hydroxyhexadecanoyl carnitine	HMDB0061642	416.3364	2.074163
Heptadecanoyl carnitine	HMDB0006210	414.3578	2.430585
Alpha-linolenyl carnitine	HMDB0006319	422.3258	2.084671
Linoleyl carnitine	HMDB0006469	424.3418	2.161335
Octadecenylcarnitine	HMDB0013338	426.3578	2.308307
Hydroxyoctadecenoylcarnitine	HMDB0013339	442.3524	2.112277
Stearoylcarnitine	HMDB0000848	428.3733	2.620369
Arachidyl carnitine	HMDB0006460	456.4044	3.051839
Docosapentaenoyl carnitine	HMDB0006321	474.3487	2.623486
Acetylcarnitine	HMDB0000201	204.123	0.6926633
Mevalonate	C00448	383.1336	1.823291
Cholesterol	C00187	387.3583	2.007833
Riboflavin	C00255	377.1461	1.791738
N-Acetyl-leucyl-leucine	C11333	287.1972	1.880555
N6-Methyl-L-lysine	C02728	161.1303	0.620004
N-Amidino-L-aspartate	C03139	176.068	0.6690886
N-Acyl-D-glutamate	C06379	175.0479	1.054438
N-Carbamyl-L-glutamate	C05829	191.0671	0.6695389
N4-(Acetyl-beta-D-glucosaminyl)asparagine	C04540	336.1458	1.856779
N-Acetyl-L-aspartate	C01042	176.0555	0.8785115
N6-N6-N6-Trimethyl-L-lysine	C03793	189.1606	0.6215123
N-Carbamoyl-L-aspartate	C00438	177.051	0.5903916
METABOLITES_END
#END