#METABOLOMICS WORKBENCH RCulpHill_20210317_102457 DATATRACK_ID:2534 STUDY_ID:ST001730 ANALYSIS_ID:AN002816 PROJECT_ID:PR001108
VERSION             	1
CREATED_ON             	March 24, 2021, 2:54 pm
#PROJECT
PR:PROJECT_TITLE                 	Mitochondrial ATP fuels ABC transporter-mediated drug efflux in cancer
PR:PROJECT_TITLE                 	chemoresistance
PR:PROJECT_SUMMARY               	Chemotherapy remains the standard of care for most cancers worldwide, however
PR:PROJECT_SUMMARY               	development of chemoresistance due to the presence of the drug-effluxing ABC
PR:PROJECT_SUMMARY               	transporters remains a significant problem. The development of safe and
PR:PROJECT_SUMMARY               	effective means to overcome chemoresistance is critical for achieving durable
PR:PROJECT_SUMMARY               	remissions in many cancer patients. We have investigated the energetic demands
PR:PROJECT_SUMMARY               	of ABC transporters in the context of the metabolic adaptations of
PR:PROJECT_SUMMARY               	chemoresistant cancer cells. Here we show that ABC transporters use
PR:PROJECT_SUMMARY               	mitochondrial-derived ATP as a source of energy to efflux drugs out of cancer
PR:PROJECT_SUMMARY               	cells. We further demonstrate that the loss of MCJ (DnaJC15), an endogenous
PR:PROJECT_SUMMARY               	negative regulator of mitochondrial respiration, in chemoresistant cancer cells
PR:PROJECT_SUMMARY               	boosts their ability to produce ATP from mitochondria and fuel ABC transporters.
PR:PROJECT_SUMMARY               	We have developed novel MCJ mimetics that can attenuate mitochondrial
PR:PROJECT_SUMMARY               	respiration and safely overcome chemoresistance in vitro and in vivo.
PR:PROJECT_SUMMARY               	Administration of MCJ mimetics in combination with standard chemotherapeutic
PR:PROJECT_SUMMARY               	drugs could therefore become an new strategy for treatment of multiple cancers.
PR:INSTITUTE                     	University of Colorado Denver
PR:DEPARTMENT                    	Biochemistry and Molecular Genetics
PR:LABORATORY                    	Angelo D'Alessandro
PR:LAST_NAME                     	Culp-Hill
PR:FIRST_NAME                    	Rachel
PR:ADDRESS                       	12801 E 17th Ave L18-9403D, Aurora, Colorado, 80045, USA
PR:EMAIL                         	rachel.hill@cuanschutz.edu
PR:PHONE                         	303-724-5798
#STUDY
ST:STUDY_TITLE                   	Mitochondrial ATP fuels ABC transporter-mediated drug efflux in cancer
ST:STUDY_TITLE                   	chemoresistance
ST:STUDY_SUMMARY                 	Chemotherapy remains the standard of care for most cancers worldwide, however
ST:STUDY_SUMMARY                 	development of chemoresistance due to the presence of the drug-effluxing ABC
ST:STUDY_SUMMARY                 	transporters remains a significant problem. The development of safe and
ST:STUDY_SUMMARY                 	effective means to overcome chemoresistance is critical for achieving durable
ST:STUDY_SUMMARY                 	remissions in many cancer patients. We have investigated the energetic demands
ST:STUDY_SUMMARY                 	of ABC transporters in the context of the metabolic adaptations of
ST:STUDY_SUMMARY                 	chemoresistant cancer cells. Here we show that ABC transporters use
ST:STUDY_SUMMARY                 	mitochondrial-derived ATP as a source of energy to efflux drugs out of cancer
ST:STUDY_SUMMARY                 	cells. We further demonstrate that the loss of MCJ (DnaJC15), an endogenous
ST:STUDY_SUMMARY                 	negative regulator of mitochondrial respiration, in chemoresistant cancer cells
ST:STUDY_SUMMARY                 	boosts their ability to produce ATP from mitochondria and fuel ABC transporters.
ST:STUDY_SUMMARY                 	We have developed novel MCJ mimetics that can attenuate mitochondrial
ST:STUDY_SUMMARY                 	respiration and safely overcome chemoresistance in vitro and in vivo.
ST:STUDY_SUMMARY                 	Administration of MCJ mimetics in combination with standard chemotherapeutic
ST:STUDY_SUMMARY                 	drugs could therefore become an new strategy for treatment of multiple cancers.
ST:INSTITUTE                     	University of Colorado Denver
ST:DEPARTMENT                    	Biochemistry and Molecular Genetics
ST:LABORATORY                    	Angelo D'Alessandro
ST:LAST_NAME                     	Culp-Hill
ST:FIRST_NAME                    	Rachel
ST:ADDRESS                       	12801 E 17th Ave L18-9403D, Aurora, Colorado, 80045, USA
ST:EMAIL                         	rachel.hill@cuanschutz.edu
ST:PHONE                         	303-724-5798
#SUBJECT
SU:SUBJECT_TYPE                  	Cultured cells
SU:SUBJECT_SPECIES               	Homo sapiens
SU:TAXONOMY_ID                   	9606
#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           	-	nci-adr-res-1	line:NCI-ADR-RES	RAW_FILE_NAME=nci-adr-res-1
SUBJECT_SAMPLE_FACTORS           	-	nci-adr-res-2	line:NCI-ADR-RES	RAW_FILE_NAME=nci-adr-res-2
SUBJECT_SAMPLE_FACTORS           	-	nci-adr-res-3	line:NCI-ADR-RES	RAW_FILE_NAME=nci-adr-res-3
SUBJECT_SAMPLE_FACTORS           	-	nci-adr-res-4	line:NCI-ADR-RES	RAW_FILE_NAME=nci-adr-res-4
SUBJECT_SAMPLE_FACTORS           	-	ovcar8-1	line:OVCAR8	RAW_FILE_NAME=ovcar8-1
SUBJECT_SAMPLE_FACTORS           	-	ovcar8-2	line:OVCAR8	RAW_FILE_NAME=ovcar8-2
SUBJECT_SAMPLE_FACTORS           	-	ovcar8-3	line:OVCAR8	RAW_FILE_NAME=ovcar8-3
SUBJECT_SAMPLE_FACTORS           	-	ovcar8-4	line:OVCAR8	RAW_FILE_NAME=ovcar8-4
#COLLECTION
CO:COLLECTION_SUMMARY            	NCI/ADR-RES (formerly MCF7/Adr) were previously described. NCI/ADR-RES cells
CO:COLLECTION_SUMMARY            	were verified to be of ovarian origin by genotyping. OVCAR-8 cells provided by
CO:COLLECTION_SUMMARY            	Dr. Ernst Lengyel at the University of Chicago. All cancer cell lines were
CO:COLLECTION_SUMMARY            	maintained in RPMI 1640 (Sigma R8758) containing glucose (2 mg/ml) and glutamine
CO:COLLECTION_SUMMARY            	(0.6 mg/ml) but no pyruvate and was supplemented with 5% Fetal calf serum.
CO:SAMPLE_TYPE                   	Cultured cells
#TREATMENT
TR:TREATMENT_SUMMARY             	N/A - compared cell lines only
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	All cancer cell lines were maintained in RPMI 1640 (Sigma R8758) containing
SP:SAMPLEPREP_SUMMARY            	glucose (2 mg/ml) and glutamine (0.6 mg/ml) but no pyruvate and was supplemented
SP:SAMPLEPREP_SUMMARY            	with 5% Fetal calf serum. Metabolic profile comparisons of OVCAR-8 and
SP:SAMPLEPREP_SUMMARY            	NCI/ADR-RES cells were performed on equal cell numbers. Cells were cultured
SP:SAMPLEPREP_SUMMARY            	under normal conditions, detached using trypsin-EDTA (0.05 %), counted,
SP:SAMPLEPREP_SUMMARY            	normalized to 0.5 x 10e6 in each sample, and cell pellets were snap frozen in
SP:SAMPLEPREP_SUMMARY            	liquid nitrogen prior to analysis. Briefly, 2 x 10e6 cells and 20μL cell media
SP:SAMPLEPREP_SUMMARY            	were extracted in 1mL and 980μL cold lysis and extraction buffer (methanol :
SP:SAMPLEPREP_SUMMARY            	acetonitrile : water, 5:3:2), respectively, and pellets were discarded.
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_SUMMARY        	Negative Mode 10 μL of water and methanol soluble fractions were run through a
CH:CHROMATOGRAPHY_SUMMARY        	Kinetex C18 1.7 μm, 100 x 2.1 mm (Phenomenex) reversed phase column (Negative
CH:CHROMATOGRAPHY_SUMMARY        	ion mode – phase A: 1 mM NH4Ac 95:5 water : acetonitrile; phase B: 1 mM NH4Ac
CH:CHROMATOGRAPHY_SUMMARY        	95:5 acetonitrile : water) via an ultra-high performance chromatographic system
CH:CHROMATOGRAPHY_SUMMARY        	(UHPLC - Vanquish, Thermo Fisher). UHPLC was coupled in line with a
CH:CHROMATOGRAPHY_SUMMARY        	high-resolution quadrupole Orbitrap instrument run in negative polarity mode
CH:CHROMATOGRAPHY_SUMMARY        	(QExactive, Thermo Fisher) at 70,000 resolution (at 200 m/z). Gradients and
CH:CHROMATOGRAPHY_SUMMARY        	other technical parameters and the variants employed herein have been
CH:CHROMATOGRAPHY_SUMMARY        	extensively described.
CH:CHROMATOGRAPHY_TYPE           	Reversed phase
CH:INSTRUMENT_NAME               	Thermo Vanquish
CH:COLUMN_NAME                   	Phenomenex Kinetex C18 (150 x 2.1mm, 2.6 um)
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:INSTRUMENT_NAME               	Thermo Q Exactive Orbitrap
MS:INSTRUMENT_TYPE               	Orbitrap
MS:MS_TYPE                       	ESI
MS:ION_MODE                      	NEGATIVE
MS:MS_COMMENTS                   	UHPLC was coupled in line with a high-resolution quadrupole Orbitrap instrument
MS:MS_COMMENTS                   	run in negative polarity mode (QExactive, Thermo Fisher) at 70,000 resolution
MS:MS_COMMENTS                   	(at 200 m/z). Gradients and other technical parameters and the variants employed
MS:MS_COMMENTS                   	herein have been extensively described.
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	Relative Abundance
MS_METABOLITE_DATA_START
Samples	nci-adr-res-1	nci-adr-res-2	nci-adr-res-3	nci-adr-res-4	ovcar8-1	ovcar8-2	ovcar8-3	ovcar8-4
Factors	line:NCI-ADR-RES	line:NCI-ADR-RES	line:NCI-ADR-RES	line:NCI-ADR-RES	line:OVCAR8	line:OVCAR8	line:OVCAR8	line:OVCAR8
ADP	6555772	6065822	5627218	5020242	1195020	1324574	1603449	1271472
Adenosine	56869	52127	62706	51022	43165	56695	64920	38247
Adenine	4681998	4823433	5343932	4569250	1855910	1827785	2208756	1771566
Guanosine	93011	110978	96284	108844	275265	594398	568583	593627
CTP	483410	422287	439497	472869	447503	721665	773763	655819
CDP	1228105	1002104	1082754	1076646	676421	703983	878290	711149
CMP	783555	781840	733690	682620	146341	129752	180992	149787
Cytidine	2031748	1953112	2140788	2093888	939895	1151636	1315728	1539288
Thymidine	305951	301790	274266	308615	186431	237766	263818	248392
Thymine	128917	126405	110512	126769	131550	114834	127277	116693
UTP	1944783	1760894	1773049	1743530	319858	612303	696481	300259
UDP	5316928	4582916	4779398	4371268	665499	697815	935314	581638
UMP	3530433	3742542	3135419	2705698	120470	149615	164491	79945
Inosine	8702914	12161080	12305680	12606760	18267070	17095970	19968730	12410890
Hypoxanthine	31389380	38631060	43306020	45223620	54848180	51187890	57504770	48006220
5-Hydroxyisourate	6600634	6845890	6129292	6672658	13074440	11204840	11933680	11254750
5-6-Dihydrothymine	1827361	1917009	1719157	1691828	1844995	2011282	2043275	1913102
UDP-glucose	3036627	2653580	2983349	2710025	1842791	1852765	1906913	1591182
Diphosphate	13250200	14018560	14756440	14311440	18897040	19043040	17841270	16779580
D-Glucose	13245630	15120110	15483060	14798540	8514636	10892060	12217580	13205660
D-Glucose 6-phosphate	965733	879319	944493	931321	720689	728885	790393	910790
D-Fructose 1-6-bisphosphate	693229	598937	648081	624524	521029	510357	577103	565111
D-Glyceraldehyde 3-phosphate/Glycerone phosphate	79993	88314	88696	93905	73940	77792	105776	106402
2/3-Phospho-D-glycerate	331029	318597	334435	363356	464036	371523	357735	391849
Pyruvate	300991	297121	283715	339693	403531	370553	376885	328033
Lactate	19984170	20611440	22715860	27923880	30321490	28519180	27757210	28896200
Maltose	78961	101403	94227	112907	71082	81829	77783	64310
Mannitol	269193	293102	287456	302170	215641	186355	245363	226844
D-Arabitol	318789	364619	343100	351264	116018	127009	158137	125711
Citrate	6144180	6624204	6092672	6558234	3894526	4806244	5379170	4769874
2-Oxoglutarate	82373	82131	71494	72471	119781	134001	142412	140057
2-Oxoglutaramate	66009	46541	101089	95699	99312	67226	95442	83971
Succinate	5051718	4632874	4694440	4474824	3089888	2754352	3435312	3081745
Fumarate	1998416	2118175	2108554	2202846	2628653	2866999	2677834	2757380
Malate	13499630	15175080	14208560	16032200	21240740	22191530	21088750	21688840
2-Hydroxyglutarate/Citramalate	110985	102400	108831	102258	158238	154510	158279	122248
D-Erythrose 4-phosphate	61257	60428	63666	67497	66071	62218	74146	87996
Sedoheptulose 1-phosphate	368576	423839	387490	400416	280751	330259	343344	341265
alpha-D-Ribose 1-phosphate	1363503	1686475	1505766	1510734	1551482	1717348	1958548	1755789
5-Oxoproline	20035530	17614330	18651800	18941670	25838820	25910490	24729090	26230150
S-Glutathionyl-L-cysteine	185201	142348	120420	226713	206357	116059	169554	110912
Ascorbate	125971	127185	131568	149338	42464	52379	64334	48230
Dehydroascorbate	155108	127602	132534	126829	154124	158130	189749	152763
gamma-L-Glutamyl-L-cysteine	2664481	2003993	2886200	2974413	1912238	2137534	2557639	2001136
S-Adenosyl-L-homocysteine	152892	198011	216287	190078	196282	175034	208810	199425
Argininosuccinate	1094164	924501	1117527	968319	925862	1207270	1214132	1369926
N-Acetylneuraminate	343068	365403	322373	426927	198429	221959	296090	358237
UDP-N-acetyl-D-glucosamine	6029590	5346558	6077392	5820928	3837310	4199980	4219220	3707591
CMP-N-acetylneuraminate	232783	204329	238756	231446	209731	211454	228466	235212
Carnosine	56911	22379	34427	36965	46879	24824	30922	31410
Phosphocreatine	55262	53067	50912	61662	150166	176380	147416	218074
N-Succinyl-L-citrulline	62440	74634	53772	64203	248718	256257	213800	278537
trans-4-Hydroxy-L-proline	3968769	4120931	4091915	4000207	2916128	3157280	3139636	3249364
Pantothenol	795363	957834	1011441	821598	1716890	1727497	1891423	1763959
Thiocysteine	1428920	1391540	1225487	1267495	1564229	1527586	1384193	1371336
Glycerol 3-phosphate	648291	1167293	898106	867120	758139	908349	1084276	2394869
Ethanolamine phosphate	92122	104421	91673	109400	214155	231923	248290	232158
Sphingosine	1582643	763672	938619	674337	182864	1438968	1664510	2142818
Acetylcholine	1866771	1837308	1891551	1690812	2493443	2728297	2598340	2220422
CDP-choline	1359205	1775477	1530045	1290695	759828	788369	1004458	516172
Sphinganine 1-phosphate	38898	36111	26141	28369	19061	29280	32577	32854
Pentanoate (valerate)	41547	40632	44074	39879	40512	48844	58257	55990
Hexanoic acid (caproate)	309251	324207	309188	301193	320974	251949	293121	321228
Heptanoic acid	103910	117553	130471	123040	146563	118003	156584	152012
Octanoic acid (caprylic acid)	453196	436075	475466	388530	492294	491560	521353	522676
Nonanoic acid (pelargonic acid)	2374261	2023772	2314727	2343822	1072073	1440051	1642882	2049484
Decanoic acid (capric acid)	732115	763066	849987	836056	317197	429200	556691	629346
Dodecanoic acid (lauric acid)	420354	543508	601562	550855	186951	279165	351478	375580
Tetradecanoic acid (myristic acid)	3512301	5204536	6482808	4864078	1710970	2418621	3310937	3833415
Hexadecanoic acid (palmitic acid)	35878000	40728450	40741760	41372540	23986310	27066920	34670920	43710380
Octadecanoic acid (stearic acid)	34812070	35356450	35678140	36534390	29785500	32249330	32618460	34393620
Tetradecenoic acid (myristoleic acid)	240638	324979	284509	326227	98558	150071	182863	211641
Hexadecenoic acid (Palmitoleic acid)	2832538	4640954	4047791	3912873	1094956	1465419	2416690	3841405
Octadecenoic acid (Oleic acid)	28583670	42149870	29823460	33395290	17230680	19074610	28926970	38732080
Linoleic acid ((9Z,12Z)-Octadecadienoic acid)	14942380	19607390	19464280	16742240	8910852	10256900	17474980	28407360
a-Linolenic acid (Octadecatrienoic acid)	471631	838270	670931	659983	223316	305805	550998	801080
Arachidonic acid (Eicosatetraenoic acid)	4813734	8177662	6548844	5157922	3094451	3274047	6217032	5973594
Stearidonic acid ((6Z,9Z,12Z,15Z)-Octadecatetraenoic acid)	15522	19990	12504	15554	13221	20215	22300	40992
Docosahexaenoic acid	1751217	2226616	2251408	2210329	1220578	1397951	2603774	2788565
Adrenic acid (7,10,13,16-Docosatetraenoic acid)	1137044	1594413	1708128	1241052	2419052	2699333	4068651	4399400
Eicosapentaenoic acid	166244	192221	179515	176588	99993	145150	272189	227376
Dihomo-gamma-linolenic acid ((8Z-11Z-14Z)-Icosatrienoic acid)	947422	1395105	1377340	1164749	597151	660778	1171155	1312168
Docosapentaenoic acid ((7Z-10Z-13Z-16Z-19Z)-Docosa-7-10-13-16-19-pentaenoic acid)	424138	532120	685695	495403	857528	1002668	1462240	1829528
Undecanoic acid	132426	153822	149023	151567	79805	95469	109453	120105
Glycochenodeoxycholate	70859	57499	45494	38720	50977	54325	74067	88128
Taurodeoxycholate/taurochenodeoxycholate/tauroursodeoxycholate	47389	37791	32388	21326	31091	31650	44134	55465
13(S)-HODE	107867	135405	119713	119528	80201	86807	121109	138328
Prostaglandin A2	11712	10754	10006	13419	6351	10697	9442	12439
Prostaglandin D2/Thromboxane A2 (isobars)	409262	448929	386805	459663	237822	285883	316394	377429
Leukotriene A4	20781	23176	23301	26241	8977	14752	14216	11759
Cholesterol sulfate	141629	109692	133520	114677	175122	200736	211723	179199
2-Methyleneglutarate	102179	89312	44661	124152	48008	32528	106176	25342
Leucocyanidin	296101	278697	405583	485330	194437	214836	291223	253157
Methylenediurea	13162700	12867100	14631040	13925980	11085980	11168300	11585540	11679420
3-Oxalomalate	5070158	5135138	4264520	4040513	6775326	5579422	6304176	5982938
2-Deoxy-alpha-D-glucoside	3054921	3400782	3062493	2801976	797638	1296303	1525692	1427221
N-Acyl-D-mannosaminolactone	375385	350169	363687	454780	97181	156837	173277	224510
N6-Methyl-L-lysine	359806	359106	337377	388175	345086	405232	414818	377839
Shikimate 3-phosphate	126734	107116	115952	144625	116999	122350	130522	111505
D-glucono-1,5-lactone	36678	28181	43772	37391	30449	31846	37924	27425
Catechin	401136	520397	582781	595374	1872750	1364505	1470464	1388229
Riboflavin	37618	49781	28185	61165	66122	64288	70586	63026
Glucosinolate	235258	260780	237203	224656	124275	154713	177612	134227
D-Ribose 5-diphosphate	149743	140498	157250	141249	121498	138867	159724	233791
S-Acylglutathione	526977	478753	390774	485706	367528	452210	365857	425410
9-Oxononanoic acid	108794	121000	134732	134852	113444	121038	114911	90511
L-Noradrenaline	757413	764735	694149	702746	627277	580290	711411	531691
N-Acetylmethionine	1631244	1717060	1833503	1828822	744468	736437	941529	923388
2-Oxo-7-methylthioheptanoic acid	155660	192478	206230	302902	264813	214152	227702	277755
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	kegg	mass	rt
ADP	C00008	426.0222	0.67181
Adenosine	C00212	268.1033	0.67937
Adenine	C00147	136.0616	0.6750599
Guanosine	C00387	284.0977	0.6756378
CTP	C00063	481.9772
CDP	C00112	402.0103	0.6030908
CMP	C00055	324.0585	0.6803118
Cytidine	C00475	242.0795	0.6416436
Thymidine	C00214	243.1003	0.6752188
Thymine	C00178	127.0499	0.6544333
UTP	C00075	482.961	0.7489136
UDP	C00015	402.9947	0.6141199
UMP	C00105	323.0283	0.6546757
Inosine	C00294	269.0872	0.678325
Hypoxanthine	C00262	137.0457	0.6787575
5-Hydroxyisourate	C11821	185.0319	0.6398596
5-6-Dihydrothymine	C00906	129.0658	0.648505
UDP-glucose	C00029	565.0475	0.603427
Diphosphate	C00013	176.9349	0.6300375
D-Glucose	C00031	179.0552	0.6673
D-Glucose 6-phosphate	C02965	259.0223	0.6244945
D-Fructose 1-6-bisphosphate	C00354	338.9886	0.6129044
D-Glyceraldehyde 3-phosphate/Glycerone phosphate	C00118	168.9893	0.628085
2/3-Phospho-D-glycerate	C00631	184.9852	1.735109
Pyruvate	C00022	87.00725	0.6584475
Lactate	C01432	89.02277	0.6785876
Maltose	C00208	341.1087	0.6615025
Mannitol	C00392	181.0704	0.6623849
D-Arabitol	C01904	151.0602	0.66036
Citrate	C00158	191.0187	0.6785351
2-Oxoglutarate	C00026	145.0131	0.672705
2-Oxoglutaramate	C00940	144.0291	0.6138319
Succinate	C00042	117.0179	0.6801701
Fumarate	C00122	115.0022	0.6705475
Malate	C00149	133.0129	0.661405
2-Hydroxyglutarate/Citramalate	C02630	147.0288	0.6695288
D-Erythrose 4-phosphate	C00279	199.0005	0.6378711
Sedoheptulose 1-phosphate	C06222	289.0328	0.6260999
alpha-D-Ribose 1-phosphate	C00620	229.0114	0.6364051
5-Oxoproline	C01879	130.0498	0.64991
S-Glutathionyl-L-cysteine	C05526	427.0938	0.6503704
Ascorbate	C00072	175.0238	0.66831
Dehydroascorbate	C05422	173.0083	0.6714271
gamma-L-Glutamyl-L-cysteine	C00669	251.069	0.6771369
S-Adenosyl-L-homocysteine	C00021	385.1278	0.674227
Argininosuccinate	C03406	291.1291	0.6448406
N-Acetylneuraminate	C00270	310.1122	0.6623605
UDP-N-acetyl-D-glucosamine	C00043	606.0743	0.6056216
CMP-N-acetylneuraminate	C00128	613.1408	0.6128405
Carnosine	C00386	227.1144	0.6135757
Phosphocreatine	C02305	212.0424	0.662325
N-Succinyl-L-citrulline
trans-4-Hydroxy-L-proline	C01157	132.0655	0.6545975
Pantothenol	C00864	218.1028	0.684045
Thiocysteine	C01962	153.9977	0.9480731
Glycerol 3-phosphate	C00093	171.0053	0.6299675
Ethanolamine phosphate	C00346	142.0263	0.663135
Sphingosine	C00319	300.2891	2.00264
Acetylcholine	C01996	146.1174	0.6640199
CDP-choline	C00307	489.1132	0.6459703
Sphinganine 1-phosphate	C01120	380.2553	1.804202
Pentanoate (valerate)	C00803	101.0593	1.73687
Hexanoic acid (caproate)	C01585	115.0752	1.231544
Heptanoic acid	C17714	129.0909	1.23364
Octanoic acid (caprylic acid)	C06423	143.1064	2.066512
Nonanoic acid (pelargonic acid)	C01601	157.1223	2.418412
Decanoic acid (capric acid)	C01571	171.138	1.963073
Dodecanoic acid (lauric acid)	C02679	199.1695	2.400162
Tetradecanoic acid (myristic acid)	C06424	227.2012	2.674048
Hexadecanoic acid (palmitic acid)	C00249	255.2327	3.083581
Octadecanoic acid (stearic acid)	C01530	283.264	3.690377
Tetradecenoic acid (myristoleic acid)	C08322	225.1853	2.489214
Hexadecenoic acid (Palmitoleic acid)	C08362	253.2171	2.723397
Octadecenoic acid (Oleic acid)	C00712	281.2484	3.131838
Linoleic acid ((9Z,12Z)-Octadecadienoic acid)	C01595	279.2327	2.785384
a-Linolenic acid (Octadecatrienoic acid)	C06427	277.2172	2.567058
Arachidonic acid (Eicosatetraenoic acid)	C00219	303.2328	2.675434
Stearidonic acid ((6Z,9Z,12Z,15Z)-Octadecatetraenoic acid)	C16300	275.2015	2.408585
Docosahexaenoic acid	C06429	327.2329	2.569912
Adrenic acid (7,10,13,16-Docosatetraenoic acid)	C16527	331.2642	2.968593
Eicosapentaenoic acid	C06428	301.2173	2.483914
Dihomo-gamma-linolenic acid ((8Z-11Z-14Z)-Icosatrienoic acid)	C03242	305.2485	2.86611
Docosapentaenoic acid ((7Z-10Z-13Z-16Z-19Z)-Docosa-7-10-13-16-19-pentaenoic acid)	C16513	329.2486	2.696104
Undecanoic acid	C17715	185.1538	2.254826
Glycochenodeoxycholate	C05466	448.3065	2.013092
Taurodeoxycholate/taurochenodeoxycholate/tauroursodeoxycholate	C05463	498.2894	1.887603
13(S)-HODE	C14762	295.2276	2.227839
Prostaglandin A2	C05953	333.2029	1.728156
Prostaglandin D2/Thromboxane A2 (isobars)	C00696	351.2205	2.25828
Leukotriene A4	C00909	317.2162	1.985211
Cholesterol sulfate	C18043	465.3044	2.623917
2-Methyleneglutarate
Leucocyanidin
Methylenediurea
3-Oxalomalate
2-Deoxy-alpha-D-glucoside
N-Acyl-D-mannosaminolactone
N6-Methyl-L-lysine
Shikimate 3-phosphate
D-glucono-1,5-lactone
Catechin
Riboflavin
Glucosinolate
D-Ribose 5-diphosphate
S-Acylglutathione
9-Oxononanoic acid
L-Noradrenaline
N-Acetylmethionine
2-Oxo-7-methylthioheptanoic acid
METABOLITES_END
#END