#METABOLOMICS WORKBENCH juliehaines_20230524_112714 DATATRACK_ID:4041 STUDY_ID:ST002714 ANALYSIS_ID:AN004399 PROJECT_ID:PR001682
VERSION             	1
CREATED_ON             	May 30, 2023, 11:59 am
#PROJECT
PR:PROJECT_TITLE                 	Loss of microglial MCT4 leads to defective synaptic pruning and anxiety-like
PR:PROJECT_TITLE                 	behavior in mice
PR:PROJECT_SUMMARY               	Microglia, the innate immune cells of the central nervous system, actively
PR:PROJECT_SUMMARY               	participate in brain development by supporting neuronal maturation and refining
PR:PROJECT_SUMMARY               	synaptic connections. These cells are emerging as highly metabolically flexible,
PR:PROJECT_SUMMARY               	able to oxidize different energetic substrates to meet their energy demand.
PR:PROJECT_SUMMARY               	Lactate is particularly abundant in the brain, but whether microglia use it as a
PR:PROJECT_SUMMARY               	metabolic fuel has been poorly explored. Here we show that microglia can import
PR:PROJECT_SUMMARY               	lactate, and this is coupled with increased lysosomal acidification. In vitro,
PR:PROJECT_SUMMARY               	loss of the monocarboxylate transporter MCT4 in microglia prevents
PR:PROJECT_SUMMARY               	lactate-induced lysosomal modulation and leads to defective cargo degradation.
PR:PROJECT_SUMMARY               	Microglial depletion of MCT4 in vivo leads to impaired synaptic pruning,
PR:PROJECT_SUMMARY               	associated with increased excitation in hippocampal neurons, enhanced E/I ratio,
PR:PROJECT_SUMMARY               	vulnerability to seizures and anxiety-like phenotype. Overall, these findings
PR:PROJECT_SUMMARY               	show that selective disruption of the MCT4 transporter in microglia is
PR:PROJECT_SUMMARY               	sufficient to alter synapse refinement and to induce defects in brain
PR:PROJECT_SUMMARY               	development and adult behavior.
PR:INSTITUTE                     	University of Colorado Denver
PR:LABORATORY                    	Lab of Angelo D'Alessandro in collaboration with lab of Rosa Paolicelli (Univ of
PR:LABORATORY                    	Lausanne)
PR:LAST_NAME                     	Haines
PR:FIRST_NAME                    	Julie
PR:ADDRESS                       	12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA
PR:EMAIL                         	julie.haines@cuanschutz.edu
PR:PHONE                         	3037243339
#STUDY
ST:STUDY_TITLE                   	Loss of microglial MCT4 leads to defective synaptic pruning and anxiety-like
ST:STUDY_TITLE                   	behavior in mice
ST:STUDY_SUMMARY                 	Microglia, the innate immune cells of the central nervous system, actively
ST:STUDY_SUMMARY                 	participate in brain development by supporting neuronal maturation and refining
ST:STUDY_SUMMARY                 	synaptic connections. These cells are emerging as highly metabolically flexible,
ST:STUDY_SUMMARY                 	able to oxidize different energetic substrates to meet their energy demand.
ST:STUDY_SUMMARY                 	Lactate is particularly abundant in the brain, but whether microglia use it as a
ST:STUDY_SUMMARY                 	metabolic fuel has been poorly explored. Here we show that microglia can import
ST:STUDY_SUMMARY                 	lactate, and this is coupled with increased lysosomal acidification. In vitro,
ST:STUDY_SUMMARY                 	loss of the monocarboxylate transporter MCT4 in microglia prevents
ST:STUDY_SUMMARY                 	lactate-induced lysosomal modulation and leads to defective cargo degradation.
ST:STUDY_SUMMARY                 	Microglial depletion of MCT4 in vivo leads to impaired synaptic pruning,
ST:STUDY_SUMMARY                 	associated with increased excitation in hippocampal neurons, enhanced E/I ratio,
ST:STUDY_SUMMARY                 	vulnerability to seizures and anxiety-like phenotype. Overall, these findings
ST:STUDY_SUMMARY                 	show that selective disruption of the MCT4 transporter in microglia is
ST:STUDY_SUMMARY                 	sufficient to alter synapse refinement and to induce defects in brain
ST:STUDY_SUMMARY                 	development and adult behavior.
ST:INSTITUTE                     	University of Colorado Denver
ST:LAST_NAME                     	Haines
ST:FIRST_NAME                    	Julie
ST:ADDRESS                       	12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA
ST:EMAIL                         	julie.haines@cuanschutz.edu
ST:PHONE                         	3037243339
#SUBJECT
SU:SUBJECT_TYPE                  	Mammal
SU:SUBJECT_SPECIES               	Mus musculus
#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           	-	1	sex:M | genetic status:KO	RAW_FILE_NAME=FC8-1
SUBJECT_SAMPLE_FACTORS           	-	2	sex:F | genetic status:WT	RAW_FILE_NAME=FC8-2
SUBJECT_SAMPLE_FACTORS           	-	3	sex:M | genetic status:WT	RAW_FILE_NAME=FC8-3
SUBJECT_SAMPLE_FACTORS           	-	4	sex:M | genetic status:KO	RAW_FILE_NAME=FC8-4
SUBJECT_SAMPLE_FACTORS           	-	5	sex:M | genetic status:WT	RAW_FILE_NAME=FC8-5
SUBJECT_SAMPLE_FACTORS           	-	6	sex:F | genetic status:KO	RAW_FILE_NAME=FC8-6
SUBJECT_SAMPLE_FACTORS           	-	7	sex:F | genetic status:KO	RAW_FILE_NAME=FC8-7
SUBJECT_SAMPLE_FACTORS           	-	8	sex:M | genetic status:WT	RAW_FILE_NAME=FC8-8
SUBJECT_SAMPLE_FACTORS           	-	9	sex:F | genetic status:WT	RAW_FILE_NAME=FC8-9
SUBJECT_SAMPLE_FACTORS           	-	10	sex:M | genetic status:KO	RAW_FILE_NAME=FC8-10
SUBJECT_SAMPLE_FACTORS           	-	11	sex:F | genetic status:KO	RAW_FILE_NAME=FC8-11
SUBJECT_SAMPLE_FACTORS           	-	12	sex:F | genetic status:KO	RAW_FILE_NAME=FC8-12
SUBJECT_SAMPLE_FACTORS           	-	13	sex:M | genetic status:WT	RAW_FILE_NAME=FC8-13
SUBJECT_SAMPLE_FACTORS           	-	14	sex:M | genetic status:KO	RAW_FILE_NAME=FC8-14
SUBJECT_SAMPLE_FACTORS           	-	15	sex:F | genetic status:KO	RAW_FILE_NAME=FC8-15
SUBJECT_SAMPLE_FACTORS           	-	1B	sex:M | genetic status:KO	RAW_FILE_NAME=FC8-16
SUBJECT_SAMPLE_FACTORS           	-	2B	sex:M | genetic status:WT	RAW_FILE_NAME=FC8-17
SUBJECT_SAMPLE_FACTORS           	-	3B	sex:M | genetic status:KO	RAW_FILE_NAME=FC8-18
SUBJECT_SAMPLE_FACTORS           	-	4B	sex:F | genetic status:WT	RAW_FILE_NAME=FC8-19
SUBJECT_SAMPLE_FACTORS           	-	5B	sex:F | genetic status:WT	RAW_FILE_NAME=FC8-20
#COLLECTION
CO:COLLECTION_SUMMARY            	Mice were bred and maintained in the animal facility of the University of
CO:COLLECTION_SUMMARY            	Lausanne. All animal experiments were authorized by “Service de la
CO:COLLECTION_SUMMARY            	consommation et des Affaires vétérinaires” (SCAV) of the Canton de Vaud in
CO:COLLECTION_SUMMARY            	Switzerland. Cx3cr1CREERT2;MCT4flox mice were obtained by crossing the
CO:COLLECTION_SUMMARY            	B6.129P2(Cg)-Cx3cr1tm2.1(cre/ERT2)Litt/WganJ mice (Cx3cr1CREERT2; No: 021160,
CO:COLLECTION_SUMMARY            	The Jackson Laboratory) with C57Bl/6.MCT4tm1flox mice (MCT4flox; kindly donated
CO:COLLECTION_SUMMARY            	by Prof. Luc Pellerin). For specific experiments, the Cx3cr1CREERT2;MCT4flox
CO:COLLECTION_SUMMARY            	line was further crossed with B6.Cg-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/J mice
CO:COLLECTION_SUMMARY            	(TdTomatoflox; No: 007914, The Jackson Laboratory). Mice were group-housed and
CO:COLLECTION_SUMMARY            	kept in a 12 h day/night cycle, with food and water ad libitum, at 20-22°C. All
CO:COLLECTION_SUMMARY            	the experiments were performed during the day cycle. Both male and female mice
CO:COLLECTION_SUMMARY            	were analyzed, unless differently specified. For in vivo gene KO induction,
CO:COLLECTION_SUMMARY            	tamoxifen (Sigma Aldrich) was prepared in 10% ethanol in corn oil at a
CO:COLLECTION_SUMMARY            	concentration of 6mg/ml. The whole litter was injected intraperitoneally (i.p.)
CO:COLLECTION_SUMMARY            	at P6 and P8 (75mg/kg). For biochemical and histological assessments, mice at
CO:COLLECTION_SUMMARY            	P15 were terminally anesthetized with sodium pentobarbital diluted in saline
CO:COLLECTION_SUMMARY            	(150mg/kg, i.p.) and perfused with cold HBSS (Life Technologies, 3ml/min). Upon
CO:COLLECTION_SUMMARY            	brain collection, the hippocampus was dissected from the right hemisphere,
CO:COLLECTION_SUMMARY            	immediately frozen in dry ice and stored at -80°C.
CO:SAMPLE_TYPE                   	Brain
#TREATMENT
TR:TREATMENT_SUMMARY             	For in vivo gene KO induction, tamoxifen (Sigma Aldrich) was prepared in 10%
TR:TREATMENT_SUMMARY             	ethanol in corn oil at a concentration of 6mg/ml. The whole litter was injected
TR:TREATMENT_SUMMARY             	intraperitoneally (i.p.) at P6 and P8 (75mg/kg).
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	Frozen tissue samples were weighed to the nearest 0.1 mg then treated with cold
SP:SAMPLEPREP_SUMMARY            	5:3:2 MeOH:acetonitrile:water to a final concentration of 15 mg/mL. Samples were
SP:SAMPLEPREP_SUMMARY            	vortexed 30 min at 4 degrees C then supernatants clarified by centrifugation (10
SP:SAMPLEPREP_SUMMARY            	min, 18,000 g, 4 degrees C) and transferred to autosampler vials.
SP:PROCESSING_STORAGE_CONDITIONS 	4℃
SP:EXTRACT_STORAGE               	-80℃
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_SUMMARY        	Negative C18
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                     	95% water 5% acetonitrile 1 mM ammonium acetate
CH:SOLVENT_B                     	95% acetonitrile 5% water 1 mM ammonium acetate
CH:FLOW_GRADIENT                 	0-0.5 min 0% B, 0.5-1.1 min 0-100% B, 1.1-2.75 min hold at 100% B, 2.75-3 min
CH:FLOW_GRADIENT                 	100-0% B, 3-5 min hold at 0% B
CH:FLOW_RATE                     	450 uL/min
CH:COLUMN_TEMPERATURE            	45
CH:SAMPLE_INJECTION              	10 uL
#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                   	Resolution 70,000, scan range 65-900 m/z, maximum injection time 200 ms,
MS:MS_COMMENTS                   	microscans 2, automatic gain control (AGC) 3 x 10^6 ions, source voltage 4.0 kV,
MS:MS_COMMENTS                   	capillary temperature 320 C, and sheath gas 45, auxiliary gas 15, and sweep gas
MS:MS_COMMENTS                   	0 (all nitrogen). Data converted to mzXML using RawConverter. Metabolites were
MS:MS_COMMENTS                   	annotated and integrated using Maven in conjunction with the KEGG database.
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	peak area
MS_METABOLITE_DATA_START
Samples	2	9	4B	5B	1	4	10	14	1B	3B	3	5	8	13	2B	6	11	12	15
Factors	sex:F | genetic status:WT	sex:F | genetic status:WT	sex:F | genetic status:WT	sex:F | genetic status:WT	sex:M | genetic status:KO	sex:M | genetic status:KO	sex:M | genetic status:KO	sex:M | genetic status:KO	sex:M | genetic status:KO	sex:M | genetic status:KO	sex:M | genetic status:WT	sex:M | genetic status:WT	sex:M | genetic status:WT	sex:M | genetic status:WT	sex:M | genetic status:WT	sex:F | genetic status:KO	sex:F | genetic status:KO	sex:F | genetic status:KO	sex:F | genetic status:KO
ATP	4068	1056	2429	1427	1386	2464	2138	1331	1697	1754	996	4291	1216	2507	2779	2872	5456	2767	2388
ADP	174204	96318	403172	186356	312636	176415	266858	229014	170798	204358	163436	276308	113801	215276	194303	172894	159564	247037	282931
Adenine	24454	14707	123822	24607	23139	18554	19909	19650	22471	27985	17750	17138	20316	23550	21226	19274	23882	17963	13142
dCMP	21739	21667	38770	28946	27051	22871	30491	25201	19950	27238	31074	24562	25167	23342	20753	16929	21680	29338	33328
dTMP	3976	5463	12142	2803	11662	3249	3227	12220	4013	4389	3568	11320	2978	10569	5261	11330	8919	13067	8566
Thymidine	31475	61772	62567	44443	68848	32711	81239	46984	23834	27501	55077	46768	62248	40667	50625	35852	57219	76814	78830
UDP	87272	202098	222751	172818	249883	89707	325420	208373	155779	425101	217664	140218	298987	265055	221572	119940	71144	312444	334756
UMP	1630021	1801532	2679521	1485859	2031066	1140998	2276923	2240977	1422959	1443761	1721796	1674128	1730714	2336480	1117313	2006782	2418894	2692203	1901694
Xanthine	662415	487166	419440	1070410	386886	795738	359160	510091	695741	839987	567921	585349	453784	641669	1708243	392454	281537	298608	538716
(S)(+)-Allantoin	392036	474487	333683	222222	318524	464562	412001	487039	251168	331801	394179	399987	378164	296109	277814	400672	408020	456428	504900
Urate	92860	27280	27475	37166	26896	39054	33700	24903	28109	34499	18226	37755	18778	33799	34669	36261	19441	19183	32213
3',5'-Cyclic AMP	17714	13335	29498	14978	19596	18520	20246	22424	15179	23659	14684	24459	21268	16982	14745	11408	18359	17209	17828
2',3'-Cyclic CMP	3753	5866	12737	6897	8135	7394	7813	4107	5986	3145	7289	4821	3564	3351	10922	5240	2900	12327	9204
5-6-Dihydrothymine	1134018	1659118	1820636	2038532	1120711	1127561	1556641	861316	1680465	1493053	1233315	1188775	1224503	972275	1668446	1143042	951298	1358746	1062685
Pyridoxamine 5'-phosphate	5325	15397	7095	16320	5639	15664	12619	7395	14753	6905	8658	8063	16982	12321	14612	5842	5487	10554	3775
UDP-glucose	973649	747962	1197260	888261	797648	1009760	1043961	1013957	984135	885720	913850	1206025	863360	1092949	828834	890863	906755	1094009	1201408
Diphosphate	2782235	2322468	3026821	3185798	2246984	2622463	2166432	2742389	2848500	2485940	2676282	2816459	1328381	1677411	3938086	2333636	2545558	2313991	2417049
D-Glucose	6369864	14164090	8062070	6349724	8031094	7653490	9410031	8279776	5208168	7092866	7073190	7493210	8872997	5731712	8413204	6555940	6326412	10622510	10192610
D-Fructose 1-6-bisphosphate	31121	11243	16365	20735	13125	30700	16317	15312	15278	30337	14573	27113	14422	122985	43232	16652	15924	19332	6464
1-3-Bisphosphoglycerate	3982	16671	13781	4089	7640	4058	9026	6630	4046	8392	7431	3904	8296	7479	2491	3096	17610	6940	8979
2/3-Phospho-D-glycerate	44300	42779	195552	44295	73139	42992	47877	50090	40450	42749	31103	54950	18351	21971	26330	34368	56979	68236	114640
Pyruvate	789865	867858	1918596	718970	683058	1284593	1024821	878040	1169054	828945	894181	835335	658627	592786	637054	761349	835259	851445	761529
Lactate	74025780	59464400	44633340	71539750	61509420	60112810	61307820	63361280	75425370	70620610	70940740	65937840	63116520	50847200	85472360	60395190	41268480	54316350	72730740
Maltose	16271	20268	7905	25615	28667	12946	16915	9791	17416	18847	11110	11251	34715	23386	19525	9385	5112	11277	14563
Mannitol	192627	207802	269635	210884	267147	217237	250142	223368	230467	252863	194773	180967	182464	185958	313102	192191	169392	219145	194984
D-Ribose	50038	40187	50286	43611	38670	49447	40390	49015	47276	67397	36622	47914	31551	52069	77459	41067	43206	38772	37934
D-Rhamnose	79499	135167	136407	99298	67074	47639	99167	90309	99400	128730	61789	50594	80978	34234	104488	61448	138837	160691	110641
D-Arabitol	74719	91796	112560	93768	96347	94103	108833	104998	102241	112166	76568	92189	76855	84682	104480	84956	83281	105927	97010
Citrate	2803388	2116640	2182521	3043761	2423268	3348617	3174525	2978397	2968153	3888857	2936611	3299230	1533486	2454023	3082795	2313846	1174778	2995822	3550006
2-Oxoglutarate	409667	371178	509002	436414	430935	303062	432364	378102	396068	542461	438916	447326	382146	435540	499373	256013	359162	470831	346524
2-Oxoglutaramate	13781	7762	11589	8570	3603	16301	11480	14033	4842	9216	9243	6181	13789	12448	2240	4374	13221	9273	9712
Succinate	667462	860569	4872072	670575	1777237	595362	1993547	770871	808324	640419	755393	721522	894370	626123	557418	626957	2844581	2688528	1921556
Fumarate	1066418	814567	955627	1168586	733482	1145712	928517	1128853	1051066	1333552	1100628	834770	641027	1030934	1264691	702226	617010	734220	878895
Malate	9060457	6461508	10078550	9595483	6720500	9279680	7847980	7971806	8917365	9871153	8795489	5880798	5055006	8511321	10066440	7025006	4315850	6075402	8339410
2-Hydroxyglutarate/Citramalate	766636	776926	877957	517767	735390	838307	847569	790506	626172	632629	708757	711883	687974	632432	509855	589020	833410	903762	838069
D-Erythrose 4-phosphate	83414	45966	37261	73980	41246	38112	51518	82023	70096	77116	46514	72897	60609	221285	67246	72224	46738	38590	36926
alpha-D-Ribose 1-phosphate	2809857	2351740	958296	2630469	2679889	1427182	3222369	3121066	2512350	2856184	1738346	2462984	2469375	3837386	2362576	2806403	2270155	2250566	2027112
S-Glutathionyl-L-cysteine	117036	92554	40698	154861	60494	75972	64763	84749	137725	192128	87258	105609	80124	100899	284346	111190	62201	65141	164250
Ascorbate	13079530	2530170	5639372	7779614	5457002	7980398	5184746	7077418	9977248	4101078	3855263	11152060	2514904	6725586	6175896	9234214	2572418	4555144	5418976
Dehydroascorbate	2324278	1824975	2705859	2204051	2378826	1684942	2337051	2036549	2262830	2757686	2514172	2435541	2079867	2355039	2754502	1469061	1905033	2267122	1770248
gamma-L-Glutamyl-D-alanine	31400	27983	24199	39612	16154	17629	18192	20651	27072	33825	23117	21530	6213	6490	38595	11502	7981	13681	18138
Bis-gamma-glutamylcystine	50233	36905	106319	25993	28473	17938	39809	57944	43361	36298	37997	76540	46143	20531	29616	64999	66849	62573	73731
5-L-Glutamyl-taurine	66171	61948	52533	60157	53568	62946	65995	58441	50622	44399	69389	78404	52047	58104	46040	44487	55988	65494	71360
3-Phosphonooxypyruvate	79876	82366	77180	63023	62991	74845	72658	72868	59725	54092	68475	92193	59043	67313	61693	77959	117038	64728	61388
N-Acetylneuraminate	1664129	1571337	2019253	1793048	1648077	1560220	1799026	1670683	1555132	1641787	1677837	1674758	1780650	1654627	1717922	1390564	1509302	1603202	1312844
alpha-D-Glucosamine 1-phosphate	51764	61179	66659	67947	44060	43058	77576	62047	66730	46809	45271	59689	62870	85235	67177	42073	53325	62578	39854
UDP-N-acetyl-D-glucosamine	1006344	698975	1050004	880268	757862	1141298	912785	924552	914199	821253	853318	1028126	806126	944465	877373	876626	884453	958555	1017610
CMP-N-acetylneuraminate	113931	79967	155622	123300	104097	147562	83555	107651	128472	127417	118701	128403	101333	111148	154877	132829	100655	120045	124868
Homocarnosine	130822	60520	429534	444561	183239	91857	98819	121579	428252	380756	79389	146952	103981	71396	347727	97489	105679	91278	89832
Carnosine	210705	156147	283423	324927	183293	105616	155796	188568	287377	322957	116550	185599	170439	132282	232381	123941	147058	166290	133708
4-Acetamidobutanoate	9649	4357	8446	3960	3353	8313	3344	6249	10958	18903	4223	8586	7508	2808	6509	3697	7197	14608	11184
N-Acetylornithine	12531	26939	26024	31017	10784	25587	18434	12864	23398	24221	25962	18068	14711	10825	30873	9372	65087	13635	15008
trans-4-Hydroxy-L-proline	4147197	3336089	5329945	4802766	3778387	4095633	3699713	3658208	4498072	4005296	3798711	3973180	3155142	3369591	4577290	4073681	3287842	3879434	3785388
Pantothenol	1314271	1714307	1724657	1169147	1922743	1741758	2058599	1468397	1326152	1467918	1298854	1499832	1813038	1822408	1667125	1573365	1567777	1779488	1626899
Pantetheine	8059	7178	3760	13145	6630	9505	4101	8873	5769	6746	9861	8241	6797	9078	12018	11502	2992	3614	7199
Taurine	159710000	182132100	149463900	167316100	164659800	186842500	187246700	147557100	158604500	162767600	185897900	165561300	165926300	163937100	171443900	164685500	147424700	170790500	150563200
5-Hydroxyindoleacetate	96889	76479	60351	105638	75715	68968	86730	88632	70010	111046	96513	76509	96995	108586	161579	64013	48099	65461	72993
quinolinic acid	354253	409269	331004	242563	315719	416915	389797	294309	302372	285473	343538	355040	273490	430830	290800	351245	309466	401051	406741
Glycerol 3-phosphate	151745	307608	130794	340027	213699	178735	304032	251564	213692	185400	187562	153859	202394	192643	187431	164302	235350	319005	728553
Ethanolamine phosphate	8159838	7577644	7419518	6045440	8091726	7159932	8253578	8669698	6135156	6139928	7903518	7954510	7471246	8330810	6864282	7767922	5658118	7984820	9510389
N-Methylethanolamine phosphate	7748	13595	11042	795	23330	11375	10152	16139	8883	9519	25060	11735	7382	8421	6001	10955	8742	28806	16787
Sphingosine 1-phosphate	23038	13137	9725	21090	17449	21271	14418	17892	24045	20143	17506	19078	20295	21156	20547	23434	10674	10363	14811
CDP-choline	10545	22131	25611	20766	13603	21537	16563	8613	29440	16100	13030	27001	9554	3716	23028	10219	7828	23862	8951
Butanoic acid	54721	64520	90195	90142	115261	49225	89797	83417	65573	108136	75857	32952	131002	123821	79251	89040	59677	101494	98235
Hexanoic acid (caproate)	196264	325061	231344	228034	330734	216418	306259	245263	240753	348030	197487	192211	421160	501912	329315	240528	340937	262716	310409
Dodecanoic acid	330050	224575	110296	180498	234882	220460	252630	213116	143197	147485	161863	338308	266875	444796	139529	234557	146941	319266	248815
Tetradecanoic acid	763444	806536	499705	745208	881928	680385	670882	751467	658972	715395	693430	849393	957210	1280626	1035345	636246	804657	771784	829414
Hexadecanoic acid	8432108	9399421	5366705	11295570	11940610	7538520	8041390	7960582	8662827	8283690	7323042	5710924	11934330	15415560	9200345	6230430	6743124	7176504	7964956
Octadecanoic acid	3661498	2803624	2273320	3691680	5052164	2641468	2706390	2222747	2505899	4375918	2895140	3894447	3423839	5243246	2851051	3332683	3240471	2976108	2428889
Tetradecenoic acid	50603	41076	31899	51203	43358	47309	34931	39698	34473	41966	33756	54865	40243	50133	32927	42212	40627	44869	42792
Octadecenoic acid	4916312	3769320	3167321	5654198	4064665	5389770	4187412	4353150	5879838	5798886	5300146	4982924	5088892	5514896	8542063	5291938	3284460	3781596	4319114
Linoleate	1009445	762524	457027	650882	717038	601433	780930	744925	638757	711324	636097	885412	891145	949693	1480590	667024	344461	798284	870816
Octadecatrienoic acid	70711	50411	34847	62517	37571	81538	50365	51577	47501	53820	51430	58828	52044	64819	65898	63660	46433	61735	64775
Eicosatetraenoic acid	7818840	5817524	3727408	8778577	5660052	6366342	5413504	6311388	7448984	11026570	4927624	7814178	7077200	8408349	16867290	5843278	6649906	4538442	5501184
Eicosapentaenoic acid	31720	25354	15459	32411	17899	41253	26785	23328	19940	29906	20045	27170	26130	30623	36783	29102	30007	31593	31727
Docosahexaenoic acid	2253824	1735175	1076797	2737675	1513043	3159823	1508382	1998411	1948757	2360035	1927849	2340664	1805036	1926539	3257455	2387292	1633724	1756368	2143392
(8Z-11Z-14Z)-Icosatrienoic acid	335456	285988	123110	242920	337073	314495	267486	289650	237824	274912	252426	333828	363290	336083	480130	260899	171219	253295	417423
(7Z-10Z-13Z-16Z-19Z)-Docosa-7-10-13-16-19-pentaenoic acid	145037	137362	91791	166847	140151	142616	121289	132400	108785	155689	134569	160946	192879	176054	342372	175141	69709	185984	149214
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	KEGG ID	m/z	medRt
ATP	C00002	505.9877	3.900415
ADP	C00008	426.0217	0.5374659
Adenine	C00147	134.0459	1.487873
dCMP	C00239	306.048	0.5384634
dTMP	C00364	321.0497	0.5930682
Thymidine	C00214	241.0814	0.6424326
UDP	C00015	402.9987	0.7927011
UMP	C00105	323.0279	0.5528081
Xanthine	C00385	151.025	0.7195943
(S)(+)-Allantoin	C02350	157.0353	0.6680162
Urate	C00366	167.0197	0.6081164
3',5'-Cyclic AMP	C00575	328.0449	0.6928797
2',3'-Cyclic CMP	C02354	304.0368	0.5317506
5-6-Dihydrothymine	C00906	127.0498	0.6443173
Pyridoxamine 5'-phosphate	C00647	247.048	0.5880014
UDP-glucose	C00029	565.0468	0.5274965
Diphosphate	C00013	176.9343	0.5713412
D-Glucose	C00031	179.0549	0.6389627
D-Fructose 1-6-bisphosphate	C00354	338.9883	0.5544744
1-3-Bisphosphoglycerate	C00236	264.9525	0.7715468
2/3-Phospho-D-glycerate	C00631	184.9845	0.5287634
Pyruvate	C00022	87.00726	0.5832267
Lactate	C01432	89.02284	0.587193
Maltose	C00208	341.1083	0.6664883
Mannitol	C00392	181.0698	0.6551488
D-Ribose	C00121	149.0451	0.6443568
D-Rhamnose	C01684	163.0601	0.6643617
D-Arabitol	C01904	151.0601	0.6628212
Citrate	C00158	191.0186	0.5606698
2-Oxoglutarate	C00026	145.0128	0.6934825
2-Oxoglutaramate	C00940	144.0289	0.5644496
Succinate	C00042	117.0177	0.5460353
Fumarate	C00122	115.0021	0.5367824
Malate	C00149	133.0127	0.5266628
2-Hydroxyglutarate/Citramalate	C02630	147.0288	0.5294623
D-Erythrose 4-phosphate	C00279	199.0004	0.5517129
alpha-D-Ribose 1-phosphate	C00620	229.0112	0.5480796
S-Glutathionyl-L-cysteine	C05526	425.08	0.56827
Ascorbate	C00072	175.0238	0.5787635
Dehydroascorbate	C05422	173.0079	0.6930554
gamma-L-Glutamyl-D-alanine	C03738	217.082	0.5780082
Bis-gamma-glutamylcystine	C03646	497.0922	0.5406611
5-L-Glutamyl-taurine	C05844	253.0493	0.5645048
3-Phosphonooxypyruvate	C03232	182.9668	0.7757728
N-Acetylneuraminate	C00270	308.0981	0.5720757
alpha-D-Glucosamine 1-phosphate	C06156	258.0378	0.5654292
UDP-N-acetyl-D-glucosamine	C00043	606.0739	0.5297859
CMP-N-acetylneuraminate	C00128	613.1389	0.5289554
Homocarnosine	C00884	239.1145	0.6844907
Carnosine	C00386	225.0985	0.6789885
4-Acetamidobutanoate	C02946	144.0653	0.6641057
N-Acetylornithine	C00437	173.0918	0.6798477
trans-4-Hydroxy-L-proline	C01157	130.0495	0.5344186
Pantothenol	C00864	218.1026	0.6525702
Pantetheine	C00831	277.1224	1.731142
Taurine	C00245	124.0059	0.6419114
5-Hydroxyindoleacetate	C05635	190.0532	0.6925029
quinolinic acid	C03722	166.0165	0.5918291
Glycerol 3-phosphate	C00093	171.0051	0.5484251
Ethanolamine phosphate	C00346	140.0105	0.5797412
N-Methylethanolamine phosphate	C01210	154.0257	0.5739992
Sphingosine 1-phosphate	C06124	378.2395	2.975569
CDP-choline	C00307	487.0992	0.5670576
Butanoic acid	C00246	87.0435	0.6664742
Hexanoic acid (caproate)	C01585	115.0751	1.733318
Dodecanoic acid	C02679	199.1696	2.316329
Tetradecanoic acid	C06424	227.2011	2.561572
Hexadecanoic acid	C00249	255.2325	2.933756
Octadecanoic acid	C01530	283.2637	3.473331
Tetradecenoic acid	C08322	225.1855	2.362523
Octadecenoic acid	C00712	281.2481	2.9763
Linoleate	C01595	279.2325	2.654063
Octadecatrienoic acid	C06427	277.2169	2.466713
Eicosatetraenoic acid	C00219	303.2325	2.556801
Eicosapentaenoic acid	C06428	301.2169	2.400344
Docosahexaenoic acid	C06429	327.2325	2.461529
(8Z-11Z-14Z)-Icosatrienoic acid	C03242	305.2482	2.735565
(7Z-10Z-13Z-16Z-19Z)-Docosa-7-10-13-16-19-pentaenoic acid	C16513	329.2484	2.654829
METABOLITES_END
#END