#METABOLOMICS WORKBENCH jgiafaglione_20230911_190913 DATATRACK_ID:4304 STUDY_ID:ST002856 ANALYSIS_ID:AN004678 PROJECT_ID:PR001788
VERSION             	1
CREATED_ON             	September 12, 2023, 2:49 pm
#PROJECT
PR:PROJECT_TITLE                 	MYC is a regulator of AR inhibition-induced metabolic requirements in prostate
PR:PROJECT_TITLE                 	cancer
PR:PROJECT_SUMMARY               	Advanced prostate cancers are treated with therapies targeting the androgen
PR:PROJECT_SUMMARY               	receptor (AR) signaling pathway. While many tumors initially respond to AR
PR:PROJECT_SUMMARY               	inhibition, nearly all develop resistance. It is critical to understand how
PR:PROJECT_SUMMARY               	prostate tumor cells respond to AR inhibition in order to exploit
PR:PROJECT_SUMMARY               	therapy-induced phenotypes prior to the outgrowth of treatment-resistant
PR:PROJECT_SUMMARY               	disease. Here, we comprehensively characterize the effect of AR blockade on
PR:PROJECT_SUMMARY               	prostate cancer metabolism using transcriptomics, metabolomics and bioenergetics
PR:PROJECT_SUMMARY               	approaches. The metabolic response to AR inhibition is defined by reduced
PR:PROJECT_SUMMARY               	glycolysis, robust elongation of mitochondria, and increased reliance on
PR:PROJECT_SUMMARY               	mitochondrial oxidative metabolism. We establish DRP1 activity and MYC signaling
PR:PROJECT_SUMMARY               	as mediators of AR blockade-induced metabolic phenotypes. Rescuing DRP1
PR:PROJECT_SUMMARY               	phosphorylation after AR inhibition restores mitochondrial fission, while
PR:PROJECT_SUMMARY               	rescuing MYC restores glycolytic activity and prevents sensitivity to complex I
PR:PROJECT_SUMMARY               	inhibition. Our study provides new insight into the regulation of
PR:PROJECT_SUMMARY               	treatment-induced metabolic phenotypes and vulnerabilities in prostate cancer.
PR:INSTITUTE                     	UCLA
PR:LABORATORY                    	Goldstein Lab
PR:LAST_NAME                     	Giafaglione
PR:FIRST_NAME                    	Jenna
PR:ADDRESS                       	610 Charles E Young Dr S, Los Angeles, CA, 90024, USA
PR:EMAIL                         	jgiafaglione@g.ucla.edu
PR:PHONE                         	408-728-3065
#STUDY
ST:STUDY_TITLE                   	Validation of on-target effect of IACS-010759 in vehicle- and
ST:STUDY_TITLE                   	Enzalutamide-treated 16D cells
ST:STUDY_SUMMARY                 	In this study, we sought to validate that 30nM IACS-010759, a complex I
ST:STUDY_SUMMARY                 	inhibitor, had an on-target effect in vehicle- and Enzalutamide-treated 16D
ST:STUDY_SUMMARY                 	prostate cancer cells.
ST:INSTITUTE                     	UCLA
ST:LABORATORY                    	Goldstein Lab
ST:LAST_NAME                     	Giafaglione
ST:FIRST_NAME                    	Jenna
ST:ADDRESS                       	610 Charles E Young Dr S, Los Angeles, CA, 90024, USA
ST:EMAIL                         	jgiafaglione@g.ucla.edu
ST:PHONE                         	408-728-3065
#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           	-	Naive-NT1	Treatment:Vehicle (DMSO)	RAW_FILE_NAME=Naive-NT1
SUBJECT_SAMPLE_FACTORS           	-	Naive-NT2	Treatment:Vehicle (DMSO)	RAW_FILE_NAME=Naive-NT2
SUBJECT_SAMPLE_FACTORS           	-	Naive-NT3	Treatment:Vehicle (DMSO)	RAW_FILE_NAME=Naive-NT3
SUBJECT_SAMPLE_FACTORS           	-	Naive-IACS-1	Treatment:30nM IACS-010759	RAW_FILE_NAME=Naive-IACS-1
SUBJECT_SAMPLE_FACTORS           	-	Naive-IACS-2	Treatment:30nM IACS-010759	RAW_FILE_NAME=Naive-IACS-2
SUBJECT_SAMPLE_FACTORS           	-	Naive-IACS-3	Treatment:30nM IACS-010759	RAW_FILE_NAME=Naive-IACS-3
SUBJECT_SAMPLE_FACTORS           	-	LT Enza-NT1	Treatment:Vehicle (DMSO)	RAW_FILE_NAME=LT Enza-NT1
SUBJECT_SAMPLE_FACTORS           	-	LT Enza-NT2	Treatment:Vehicle (DMSO)	RAW_FILE_NAME=LT Enza-NT2
SUBJECT_SAMPLE_FACTORS           	-	LT Enza-NT3	Treatment:Vehicle (DMSO)	RAW_FILE_NAME=LT Enza-NT3
SUBJECT_SAMPLE_FACTORS           	-	LT Enza-IACS-1	Treatment:30nM IACS-010759	RAW_FILE_NAME=LT Enza-IACS-1
SUBJECT_SAMPLE_FACTORS           	-	LT Enza-IACS-2	Treatment:30nM IACS-010759	RAW_FILE_NAME=LT Enza-IACS-2
SUBJECT_SAMPLE_FACTORS           	-	LT Enza-IACS-3	Treatment:30nM IACS-010759	RAW_FILE_NAME=LT Enza-IACS-3
#COLLECTION
CO:COLLECTION_SUMMARY            	Vehicle- and Enzalutamide-treated 16D cells were cultured with 30nM IACS-010759
CO:COLLECTION_SUMMARY            	for 24 hours
CO:SAMPLE_TYPE                   	Cultured cells
#TREATMENT
TR:TREATMENT_SUMMARY             	Vehicle- and Enzalutamide-treated 16D cells were cultured with 30nM IACS-010759
TR:TREATMENT_SUMMARY             	in U13C-glucose-containing media for 24 hours
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	Cell plates were placed on ice and quickly washed with ice-cold 0.9% (w/v) NaCl.
SP:SAMPLEPREP_SUMMARY            	Cells were immediately treated with 500 μL of ice-cold MeOH and 200 μL water
SP:SAMPLEPREP_SUMMARY            	containing 1 μg of the internal standard norvaline. Cells were then scraped and
SP:SAMPLEPREP_SUMMARY            	placed in 1.5 mL centrifuge tubes kept on ice. Next, 500 μL of chloroform was
SP:SAMPLEPREP_SUMMARY            	added, after which samples were vortexed for 1 minute and then spun at 10,000g
SP:SAMPLEPREP_SUMMARY            	for 5 minutes at 4C. The aqueous layer was transferred to a GC/MS sample vial
SP:SAMPLEPREP_SUMMARY            	and dried overnight using a refrigerated CentriVap.
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_TYPE           	GC
CH:INSTRUMENT_NAME               	Agilent 7890A
CH:COLUMN_NAME                   	Agilent DB5-MS (30m x 0.25mm, 0.25um)
CH:SOLVENT_A                     	N/A (GC-MS)
CH:SOLVENT_B                     	N/A (GC-MS)
CH:FLOW_GRADIENT                 	N/A (GC-MS)
CH:FLOW_RATE                     	1 ml/min
CH:COLUMN_TEMPERATURE            	23
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:INSTRUMENT_NAME               	Agilent 5977B
MS:INSTRUMENT_TYPE               	GC-TOF
MS:MS_TYPE                       	EI
MS:ION_MODE                      	POSITIVE
MS:MS_COMMENTS                   	Data was analyzed using Agilent MassHunter software. Stable isotope tracing data
MS:MS_COMMENTS                   	was corrected for natural abundance of heavy isotopes with FluxFix software
MS:MS_COMMENTS                   	using a reference set of unlabeled metabolite standards2.
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	abundance
MS_METABOLITE_DATA_START
Samples	LT Enza-IACS-1	LT Enza-IACS-2	LT Enza-IACS-3	LT Enza-NT1	LT Enza-NT2	LT Enza-NT3	Naive-IACS-1	Naive-IACS-2	Naive-IACS-3	Naive-NT1	Naive-NT2	Naive-NT3
Factors	Treatment:30nM IACS-010759	Treatment:30nM IACS-010759	Treatment:30nM IACS-010759	Treatment:Vehicle (DMSO)	Treatment:Vehicle (DMSO)	Treatment:Vehicle (DMSO)	Treatment:30nM IACS-010759	Treatment:30nM IACS-010759	Treatment:30nM IACS-010759	Treatment:Vehicle (DMSO)	Treatment:Vehicle (DMSO)	Treatment:Vehicle (DMSO)
a-Ketoglutarate(M0)	99792	106227	27397	16501	45395	15677	109019	163257	236113	57764	65165	55183
a-Ketoglutarate(M1)	27012	29811	7399	6334	17293	6327	28521	42532	62072	18109	20578	17510
a-Ketoglutarate(M2)	17391	17326	4525	7450	20759	7297	14758	21905	31372	23562	26476	22126
a-Ketoglutarate(M3)	5004	4888	1290	2885	8369	2925	3355	4886	7049	8694	10250	8141
a-Ketoglutarate(M4)	2280	2057	468	1504	4474	1572	1149	1792	2942	5683	6280	4911
a-Ketoglutarate(M5)	887	497	236	584	1720	531	480	623	824	2195	2485	2036
a-Ketoglutarate(M6)	2260	206	158	197	1586	356	139	144	229	649	678	651
Alanine260(M0)	347992	304246	127124	215690	493745	300897	190886	248095	344244	474138	543040	475509
Alanine260(M1)	84950	74185	31090	52690	120919	73435	46972	61016	84438	120178	136954	119851
Alanine260(M2)	50668	47518	19364	26996	62778	37530	30655	38658	52604	71447	80192	70174
Alanine260(M3)	414036	409583	176339	107178	249742	150091	279888	368704	504625	474792	546152	460254
Alanine260(M4)	81616	80654	34541	20783	48753	29305	55029	72583	99197	93635	108125	91382
Asparagine(M0)	1009566	895924	239743	277551	846800	472191	596242	824483	1141523	770563	904853	735327
Asparagine(M1)	378186	333547	86528	101076	316461	174011	219235	306109	427761	285676	337770	272437
Asparagine(M2)	177273	155219	39939	47764	149812	82321	101807	141772	199196	134608	158848	128790
Asparagine(M3)	44832	39529	10173	11725	36870	19857	25054	35035	48983	32799	38387	31336
Asparagine(M4)	10765	9469	2490	2766	9068	4966	6114	8415	11697	7816	9151	7411
Asparagine(M5)	2090	1915	525	562	1958	918	1137	1494	2091	1446	1728	1541
Aspartate418(M0)	195550	197609	48245	82575	237275	143991	64890	87671	134395	232148	261238	210047
Aspartate418(M1)	71574	70933	16735	35205	102818	61929	23208	31407	47498	97421	109980	88244
Aspartate418(M2)	40702	36894	8752	25167	73247	43587	12642	15910	24828	82784	94530	75720
Aspartate418(M3)	25728	30826	6797	11771	34148	20208	10268	12245	18548	47855	53815	42252
Aspartate418(M4)	8355	9605	2104	4414	12837	7599	3250	3873	5863	19736	22345	17571
Aspartate418(M5)	2994	3760	778	1371	3891	2330	1376	1517	2254	6330	7250	5684
Citrate459(M0)	259696	194777	33887	199299	522614	341684	98254	132349	192898	505142	535640	449210
Citrate459(M1)	108572	74133	12946	97653	261469	170281	39001	50164	74062	236628	250774	208074
Citrate459(M2)	114201	55734	8366	124291	336339	219868	38206	40431	59647	467196	497097	405808
Citrate459(M3)	50502	22718	3402	60302	166903	107257	16912	17148	25433	225645	239952	194992
Citrate459(M4)	27676	10173	1488	35105	96256	62456	9020	8256	11972	162560	173046	138143
Citrate459(M5)	12763	4783	732	14958	42257	27081	4452	4149	5898	82315	87262	68759
Citrate459(M6)	4683	1913	276	5408	15157	9903	1892	1635	2177	33007	34714	26838
Citrate459(M7)	1729	1276	632	2255	5044	3333	1077	1170	1596	10841	11417	9104
Citrate591(M0)	48875	35782	6401	36480	99889	63921	17832	24072	34804	96233	101381	84538
Citrate591(M1)	25641	17953	3176	21972	59866	38570	9204	12002	17868	55266	58304	47913
Citrate591(M2)	24604	12854	2187	25551	71079	45349	8414	9053	13530	93010	99326	80898
Citrate591(M3)	12295	5536	776	14148	38540	24966	4140	4081	6400	50983	55183	44282
Citrate591(M4)	6647	2662	358	8080	22688	14291	2295	2009	2985	35429	38247	30190
Citrate591(M5)	3122	1102	212	3644	10424	6623	1052	1026	1436	18881	19719	15869
Citrate591(M6)	1251	414	78	1375	3924	2646	437	368	518	8188	8632	6775
Citrate591(M7)	429	171	18	549	1363	893	172	142	190	2901	3055	2409
Cysteine(M0)	23428	25676	1385	1318	6895	1373	6104	27600	28239	3847	6472	7644
Cysteine(M1)	8038	8917	477	519	2345	455	2143	9831	9880	1245	2004	2558
Cysteine(M2)	4830	5118	282	176	1385	197	1175	5726	5773	746	1204	1487
Cysteine(M3)	1628	1378	157	115	611	164	316	1565	1649	217	461	620
Cysteine(M4)	492	426	34	52	328	41	42	434	538	107	102	220
Fumarate(M0)	297423	345604	120547	45649	105267	64798	203366	282960	384063	182440	208741	172595
Fumarate(M1)	73693	84908	30144	15047	35614	21806	50078	69196	94011	55822	64273	52640
Fumarate(M2)	43235	46509	16624	12057	29714	18096	26973	36790	50178	55348	63541	50658
Fumarate(M3)	58852	60773	23936	5025	13648	8100	39397	56524	75943	29420	33113	26731
Fumarate(M4)	15426	21060	7391	2974	7867	5085	11059	13904	19153	13414	14313	11549
Fumarate(M5)	5292	7258	2435	627	1462	1062	3801	4966	7090	3167	3548	2610
GABA(M0)	27975	29870	7247	3731	15089	7153	17984	25165	40459	8093	17940	13949
GABA(M1)	6219	5876	1501	649	3228	1440	3872	5669	8598	1727	3997	2999
GABA(M2)	2640	2933	593	262	1498	566	1846	2531	3701	705	1453	1362
GABA(M3)	732	1124	376	1855	474	2344	2573	2328	2299	491	515	377
GABA(M4)	273	411	155	277	374	298	933	1225	1032	318	264	559
GABA(M5)	131	138	429	188	205	447	332	184	156	498	41	115
Glutamate432(M0)	2147649	2202498	718099	886558	2273429	1382455	1288339	1719802	2362496	1588360	1822097	1531879
Glutamate432(M1)	852865	848532	266843	438353	1149927	692062	488485	652815	905766	684174	790570	658296
Glutamate432(M2)	603646	543616	166578	490676	1308822	786124	283478	362904	505833	801539	924647	759431
Glutamate432(M3)	215559	180541	54028	230336	626680	373980	85226	104504	145835	361911	417552	337641
Glutamate432(M4)	96538	74831	21972	122981	338800	201539	33020	37250	51858	220095	253560	201624
Glutamate432(M5)	37146	28896	8683	46541	129374	77408	11295	12184	16707	93089	107918	84420
Glutamate432(M6)	10982	8629	2558	14235	39788	23753	3160	3432	4702	29840	34398	27046
Isoleucine274(M0)	161724	166539	52166	51963	153622	128328	100803	134061	210366	124092	169851	121935
Isoleucine274(M1)	42539	43741	13706	12019	40515	33754	26436	34983	55797	32529	44776	32173
Isoleucine274(M2)	15114	16711	5608	4943	15552	12603	9959	13368	21237	12428	17142	11773
Isoleucine274(M3)	2763	2974	870	833	2737	2204	1758	2428	3529	2139	2951	1901
Isoleucine274(M4)	705	537	933	52	1494	860	326	513	912	435	587	454
Isoleucine274(M5)	128	74	73		188	97	166	144	148	89	57	160
Isoleucine274(M6)	122	39	39	213	60	68	35	21	37		46	26
Isoleucine274(M7)	28		47		22			323	128	1206		
Itaconate(M0)	1244	3973	808	11754	1111	964	1150	917	1041	1478	1282	648
Itaconate(M1)	249	1364	3849	3381	5684	4092	4893	4223	5014	5384	282	325
Itaconate(M2)	5506	3509	4229	4591	4839	4958	3857	4479	5665	656	5076	4099
Itaconate(M3)	3504	1893	2269	2328	2392	2393	1292	2255	3132	2189	2161	2469
Itaconate(M4)	578929	167230	359099	383383	361021	432142	178991	319433	475830	240941	328553	380785
Itaconate(M5)	152438	43195	93278	100113	94321	113133	46409	83437	124146	62380	85585	100581
Itaconate(M6)	42121	5066	3474	3764	4542	3050	5282	3861	35245	3923	4230	3968
KIC (M0)	18686	19489	5533	4787	13926	4635	24363	32599	51708	10221	9742	10955
KIC (M1)	2659	2965	1004	1056	1792	483	3397	4629	8141	1662	1263	1359
KIC (M2)	893	1309	428	293	724	328	1125	1538	2753	400	661	853
KIC (M3)	1640	1985	104	1403	2086	72	1790	105	282	75	1431	1566
KIC (M4)	329	23	60	40	490	11	133	463	299	255	56	362
KIC (M5)	1131	2051	63	622	1244	520	2066	831	870	1249	1540	807
KIC (M6)	2355	2720	2372	2360	3208	2018	2119	2127	1794	1812	2011	2182
KIC (M7)	379	79	53	63	43	409	522	435	443	73		24
KIV (M0)	807	969	614	600	589	766	907	737	1915	493	281	925
KMV(M0)	14310	16931	8918	6320	13204	6124	15747	21836	32382	10312	12261	11733
Lactate261(M0)	1196661	971763	439592	331918	1105297	948370	1097993	1719796	2143845	793387	800079	611706
Lactate261(M1)	277408	224940	100266	79000	257610	218026	254832	398785	501223	189498	190570	147506
Lactate261(M2)	174602	157367	66850	41195	124674	105463	192178	277244	362144	120748	123928	101477
Lactate261(M3)	1374233	1461494	618121	146085	274459	152882	2076662	2765173	3840234	770592	808819	723843
Lactate261(M4)	272848	292006	121707	28625	52385	28345	420230	562633	796239	151918	160304	143161
Leucine 274 (M0)	233755	244519	83763	83814	240761	201785	142420	188062	284248	170784	231946	173355
Leucine 274 (M1)	58850	61438	20620	20735	60338	50592	35086	47371	72048	42724	58289	43668
Leucine 274 (M2)	22889	23498	7866	8068	24561	19536	13738	18050	27428	16913	24238	17414
Leucine 274 (M3)	3720	3889	1336	1346	4164	3187	2214	3014	4646	2772	4167	3053
Leucine 274 (M4)	713	535	308	190	985	495	464	977	1239	704	1195	496
Leucine 274 (M5)	767	493	700	344	607	787	894	453	791	654	705	580
Leucine 274 (M6)	3285	4357	2755	3047	4567	2600	3601	4186	4598	2878	4335	3553
Malate(M0)	489598	558136	193726	48496	139821	80332	358903	477570	646897	301571	333139	277949
Malate(M1)	178287	201971	68283	22731	66644	37905	128550	172170	234019	129174	142516	118226
Malate(M2)	109575	118055	40435	19785	59139	34512	72826	96926	130322	124378	136184	110903
Malate(M3)	118795	136116	48078	10193	30694	17611	85973	114705	153074	71447	77712	62736
Malate(M4)	38174	43348	15218	4125	12591	7061	26740	35958	47579	30705	33435	26641
Malate(M5)	15753	18288	6520	1304	3936	2267	11468	15250	20152	10110	10969	8664
Methionine320(M0)	69564	67708	18714	22342	75146	52193	36913	50339	79600	47115	65481	50128
Methionine320(M1)	17792	17477	4799	5883	19560	13551	9649	12943	20731	12345	17000	13009
Methionine320(M2)	9981	10309	2750	3334	10771	7598	5469	7259	11512	6826	9441	7170
Methionine320(M3)	2155	2244	503	668	2230	1586	1244	1483	2514	1450	2103	1494
Methionine320(M4)	1050	1036	256	387	1268	877	891	1197	1866	1236	1843	1321
Methionine320(M5)	215	196	158	314	469	377	334	332	400	389	561	377
Methionine320(M6)	89	70	70	34	25	103	170	169	140	162	190	144
N-AcetylAspartate(M0)	1312318	1465725	469880	698030	1773597	1104964	203049	270212	388504	579161	628760	510252
N-AcetylAspartate(M1)	376624	399676	122563	214055	556580	358112	55119	69533	102612	186297	202245	160899
N-AcetylAspartate(M2)	227972	223009	60683	178112	461964	291904	44726	48022	74073	282207	292435	231835
N-AcetylAspartate(M3)	136234	146987	44002	61750	158462	101326	33844	41876	59157	103187	108891	83151
N-AcetylAspartate(M4)	36776	36982	10812	28767	73277	47630	10613	11604	17899	62130	66890	51047
N-AcetylAspartate(M5)	17284	18765	5723	9939	25307	16488	5757	6750	9607	25507	27374	20963
Norvaline 260(M0)	3974877	3962784	1827885	1703480	3679113	3189396	2534652	3159229	3991789	2660455	3217247	2659020
Norvaline 260(M1)	1092441	1090942	490306	450636	1007972	859518	681138	857863	1101177	717103	875987	715646
Norvaline 260(M2)	409565	410397	183977	171562	377992	325551	255240	321875	411512	267778	327993	267359
Norvaline 260(M3)	66754	67039	32200	29574	62204	53367	42607	52818	66920	44044	53443	43284
Norvaline 288(M0)	3265341	3270719	1477085	1342339	2996590	2601310	2036278	2563583	3277615	2135918	2607973	2132606
Norvaline 288(M1)	869910	870560	381062	345706	793735	683579	529887	672706	872733	557823	686216	555317
Norvaline 288(M2)	337419	336360	149980	135525	308021	264648	206069	260697	338043	216206	266058	216583
Norvaline 288(M3)	53065	52762	23816	21663	48394	41673	32647	41289	53551	34010	41445	34314
Ornithine474(M0)	5268	5218	713	573	3286	1330	3545	5660	9911	1115	2670	1964
Ornithine474(M1)	2207	2120	315	233	1289	472	1523	2306	4025	451	1000	801
Ornithine474(M2)	987	1007	151	101	588	239	577	1086	1791	246	496	417
Ornithine474(M3)	296	219	67	118	165	77	150	282	442	44	107	43
Ornithine474(M4)	59	47	35	72	18	16	45	63	125	10	13	20
Ornithine474(M5)	50	9	6	20	245	10	14	57	33	85	20	55
Ornithine474(M6)	683	465	163	28	320	184	9	329	203	16	34	24
Pyruvate(M0)	215579	206392	104245	124663	270083	151032	169389	220542	232331	235060	206784	178005
Pyruvate(M1)	22902	34190	21111	13567	42867	28332	17785	24570	37003	27181	33432	30336
Pyruvate(M2)	9067	11820	2891	9013	17306	8543	15333	12102	19293	20768	13292	12494
Pyruvate(M3)	82914	93994	31765	31924	49440	21493	139003	179940	265334	163389	141305	130490
Pyruvate(M4)	6822	6800	4552	2022	7206	794	10849	17939	21631	13136	11239	11401
Serine390(M0)	1323279	1307215	540211	582180	1350869	805170	850988	1090835	1425068	1038591	1160357	968192
Serine390(M1)	557195	553634	226446	231654	542200	321127	375476	483343	635340	454989	508105	419082
Serine390(M2)	312322	312737	126802	123011	289015	170704	221166	285704	375925	261392	292918	240036
Serine390(M3)	125924	110499	44418	60736	141510	83850	111519	139268	182578	254294	285846	232663
Serine390(M4)	37680	32626	12958	17678	41457	24514	34010	42282	55840	77665	87828	70969
Succinate(M0)	115272	1075985	59855	56283	131426	72058	90905	87326	118003	129255	130210	100195
Succinate(M1)	27882	260454	14084	15538	37248	20714	21454	20586	26771	33209	34919	26885
Succinate(M2)	14959	112383	6347	10138	25455	14760	9689	9506	12890	26674	29434	21770
Succinate(M3)	3367	17855	1155	3050	7800	4698	1913	1935	2577	9283	10123	7727
Succinate(M4)	1491	4180	680	1697	3695	2352	1055	1189	1368	4014	4746	3793
Succinate(M5)	412	662	248	345	932	630	263	267	216	932	1115	1100
Threonine404(M0)	115134	128562	28728	29033	109256	39902	68795	125115	149722	111856	118510	99986
Threonine404(M1)	40278	45002	10035	10167	38341	14117	23891	43292	52362	39666	41514	35129
Threonine404(M2)	20842	22999	5269	5266	19398	7243	12092	21085	25146	18468	20061	16676
Threonine404(M3)	5043	5513	1380	1073	4672	1764	3044	4901	6083	4292	4659	3943
Threonine404(M4)	1310	1580	290	243	1030	371	732	1280	1455	965	1233	930
Threonine404(M5)	289	236	91	52	207	130	141	237	204	272	179	172
Urea(M0)	543176	461669	465	531	1048292	273828	74405	422136	516481	346239	403927	257679
Urea(M1)	111405	32042	558	620	217563	56156	40523	86696	106745	71630	30523	53855
Valine288(M0)	91415	93209	33420	27370	82301	51486	56761	76732	114600	62324	78346	62725
Valine288(M1)	22477	23200	8199	6872	20577	12462	14013	18581	28361	15215	19250	15120
Valine288(M2)	9038	8882	3189	2751	7995	4994	5676	7468	11073	6212	7472	6058
Valine288(M3)	1480	1459	502	459	1324	821	875	1121	1667	965	1224	1062
Valine288(M4)	198	194	82	79	205	154	162	129	303	119	195	196
Valine288(M5)	525	558	404	434	585	451	550	464	571	455	547	493
Valine288(M6)	133	171	13		10	19	27	98	124	16	103	171
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name
a-Ketoglutarate(M0)
a-Ketoglutarate(M1)
a-Ketoglutarate(M2)
a-Ketoglutarate(M3)
a-Ketoglutarate(M4)
a-Ketoglutarate(M5)
a-Ketoglutarate(M6)
Alanine260(M0)
Alanine260(M1)
Alanine260(M2)
Alanine260(M3)
Alanine260(M4)
Asparagine(M0)
Asparagine(M1)
Asparagine(M2)
Asparagine(M3)
Asparagine(M4)
Asparagine(M5)
Aspartate418(M0)
Aspartate418(M1)
Aspartate418(M2)
Aspartate418(M3)
Aspartate418(M4)
Aspartate418(M5)
Citrate459(M0)
Citrate459(M1)
Citrate459(M2)
Citrate459(M3)
Citrate459(M4)
Citrate459(M5)
Citrate459(M6)
Citrate459(M7)
Citrate591(M0)
Citrate591(M1)
Citrate591(M2)
Citrate591(M3)
Citrate591(M4)
Citrate591(M5)
Citrate591(M6)
Citrate591(M7)
Cysteine(M0)
Cysteine(M1)
Cysteine(M2)
Cysteine(M3)
Cysteine(M4)
Fumarate(M0)
Fumarate(M1)
Fumarate(M2)
Fumarate(M3)
Fumarate(M4)
Fumarate(M5)
GABA(M0)
GABA(M1)
GABA(M2)
GABA(M3)
GABA(M4)
GABA(M5)
Glutamate432(M0)
Glutamate432(M1)
Glutamate432(M2)
Glutamate432(M3)
Glutamate432(M4)
Glutamate432(M5)
Glutamate432(M6)
Isoleucine274(M0)
Isoleucine274(M1)
Isoleucine274(M2)
Isoleucine274(M3)
Isoleucine274(M4)
Isoleucine274(M5)
Isoleucine274(M6)
Isoleucine274(M7)
Itaconate(M0)
Itaconate(M1)
Itaconate(M2)
Itaconate(M3)
Itaconate(M4)
Itaconate(M5)
Itaconate(M6)
KIC (M0)
KIC (M1)
KIC (M2)
KIC (M3)
KIC (M4)
KIC (M5)
KIC (M6)
KIC (M7)
KIV (M0)
KMV(M0)
Lactate261(M0)
Lactate261(M1)
Lactate261(M2)
Lactate261(M3)
Lactate261(M4)
Leucine 274 (M0)
Leucine 274 (M1)
Leucine 274 (M2)
Leucine 274 (M3)
Leucine 274 (M4)
Leucine 274 (M5)
Leucine 274 (M6)
Malate(M0)
Malate(M1)
Malate(M2)
Malate(M3)
Malate(M4)
Malate(M5)
Methionine320(M0)
Methionine320(M1)
Methionine320(M2)
Methionine320(M3)
Methionine320(M4)
Methionine320(M5)
Methionine320(M6)
N-AcetylAspartate(M0)
N-AcetylAspartate(M1)
N-AcetylAspartate(M2)
N-AcetylAspartate(M3)
N-AcetylAspartate(M4)
N-AcetylAspartate(M5)
Norvaline 260(M0)
Norvaline 260(M1)
Norvaline 260(M2)
Norvaline 260(M3)
Norvaline 288(M0)
Norvaline 288(M1)
Norvaline 288(M2)
Norvaline 288(M3)
Ornithine474(M0)
Ornithine474(M1)
Ornithine474(M2)
Ornithine474(M3)
Ornithine474(M4)
Ornithine474(M5)
Ornithine474(M6)
Pyruvate(M0)
Pyruvate(M1)
Pyruvate(M2)
Pyruvate(M3)
Pyruvate(M4)
Serine390(M0)
Serine390(M1)
Serine390(M2)
Serine390(M3)
Serine390(M4)
Succinate(M0)
Succinate(M1)
Succinate(M2)
Succinate(M3)
Succinate(M4)
Succinate(M5)
Threonine404(M0)
Threonine404(M1)
Threonine404(M2)
Threonine404(M3)
Threonine404(M4)
Threonine404(M5)
Urea(M0)
Urea(M1)
Valine288(M0)
Valine288(M1)
Valine288(M2)
Valine288(M3)
Valine288(M4)
Valine288(M5)
Valine288(M6)
METABOLITES_END
#END