#METABOLOMICS WORKBENCH hik2004_20240301_110003 DATATRACK_ID:4684 STUDY_ID:ST003118 ANALYSIS_ID:AN005112 PROJECT_ID:PR001934
VERSION             	1
CREATED_ON             	March 8, 2024, 9:58 am
#PROJECT
PR:PROJECT_TITLE                 	Glucose Hypometabolism Prompts RAN Translation and Exacerbates C9orf72-related
PR:PROJECT_TITLE                 	ALS/FTD Phenotypes
PR:PROJECT_SUMMARY               	The most prevalent genetic cause of both amyotrophic lateral sclerosis and
PR:PROJECT_SUMMARY               	frontotemporal dementia is a (GGGGCC)n nucleotide repeat expansion (NRE)
PR:PROJECT_SUMMARY               	occurring in the first intron of the C9orf72 gene (C9). Brain glucose
PR:PROJECT_SUMMARY               	hypometabolism is consistently observed in C9-NRE carriers, even at
PR:PROJECT_SUMMARY               	pre-symptomatic stages, although its potential role in disease pathogenesis is
PR:PROJECT_SUMMARY               	unknown. Here, we identified alterations in glucose metabolic pathways and ATP
PR:PROJECT_SUMMARY               	levels in the brains of asymptomatic C9-BAC mice. We found that, through
PR:PROJECT_SUMMARY               	activation of the GCN2 kinase, glucose hypometabolism drives the production of
PR:PROJECT_SUMMARY               	dipeptide repeat proteins (DPRs), impairs the survival of C9 patient-derived
PR:PROJECT_SUMMARY               	neurons, and triggers motor dysfunction in C9-BAC mice. We also found that one
PR:PROJECT_SUMMARY               	of the arginine-rich DPRs (PR) can directly contribute to glucose metabolism and
PR:PROJECT_SUMMARY               	metabolic stress. These findings provide a potential mechanistic link between
PR:PROJECT_SUMMARY               	energy imbalances and C9-ALS/FTD pathogenesis and suggest
PR:INSTITUTE                     	Thomas Jefferson University
PR:LAST_NAME                     	Trotti
PR:FIRST_NAME                    	Davide
PR:ADDRESS                       	900 Walnut Street, Philadelphia PA 19107
PR:EMAIL                         	davide.trotti@jefferson.edu
PR:PHONE                         	215-955-8416
#STUDY
ST:STUDY_TITLE                   	Glucose Hypometabolism Prompts RAN Translation and Exacerbates C9orf72-related
ST:STUDY_TITLE                   	ALS/FTD Phenotypes - Study 2
ST:STUDY_SUMMARY                 	The most prevalent genetic cause of both amyotrophic lateral sclerosis and
ST:STUDY_SUMMARY                 	frontotemporal dementia is a (GGGGCC)n nucleotide repeat expansion (NRE)
ST:STUDY_SUMMARY                 	occurring in the first intron of the C9orf72 gene (C9). Brain glucose
ST:STUDY_SUMMARY                 	hypometabolism is consistently observed in C9-NRE carriers, even at
ST:STUDY_SUMMARY                 	pre-symptomatic stages, although its potential role in disease pathogenesis is
ST:STUDY_SUMMARY                 	unknown. Here, we identified alterations in glucose metabolic pathways and ATP
ST:STUDY_SUMMARY                 	levels in the brains of asymptomatic C9-BAC mice. We found that, through
ST:STUDY_SUMMARY                 	activation of the GCN2 kinase, glucose hypometabolism drives the production of
ST:STUDY_SUMMARY                 	dipeptide repeat proteins (DPRs), impairs the survival of C9 patient-derived
ST:STUDY_SUMMARY                 	neurons, and triggers motor dysfunction in C9-BAC mice. We also found that one
ST:STUDY_SUMMARY                 	of the arginine-rich DPRs (PR) can directly contribute to glucose metabolism and
ST:STUDY_SUMMARY                 	metabolic stress. These findings provide a potential mechanistic link between
ST:STUDY_SUMMARY                 	energy imbalances and C9-ALS/FTD pathogenesis and suggest a feedforward loop
ST:STUDY_SUMMARY                 	model that opens several opportunities for therapeutic intervention.
ST:INSTITUTE                     	Thomas Jefferson University
ST:LAST_NAME                     	Trotti
ST:FIRST_NAME                    	Davide
ST:ADDRESS                       	900 Walnut Street, Philadelphia, PA 19107, USA
ST:EMAIL                         	davide.trotti@jefferson.edu
ST:PHONE                         	215-955-8416
#SUBJECT
SU:SUBJECT_TYPE                  	Mammal
SU:SUBJECT_SPECIES               	Mus musculus
SU:TAXONOMY_ID                   	10090
#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           	-	2DG_1	Sample source:Brain | Treatment:2DG	Genotype=WT; RAW_FILE_NAME(Raw File Name)=2DG_1.raw
SUBJECT_SAMPLE_FACTORS           	-	2DG_2	Sample source:Brain | Treatment:2DG	Genotype=WT; RAW_FILE_NAME(Raw File Name)=2DG_2.raw
SUBJECT_SAMPLE_FACTORS           	-	2DG_3	Sample source:Brain | Treatment:2DG	Genotype=WT; RAW_FILE_NAME(Raw File Name)=2DG_3.raw
SUBJECT_SAMPLE_FACTORS           	-	2DG_4	Sample source:Brain | Treatment:2DG	Genotype=WT; RAW_FILE_NAME(Raw File Name)=2DG_4.raw
SUBJECT_SAMPLE_FACTORS           	-	2DG_5	Sample source:Brain | Treatment:2DG	Genotype=WT; RAW_FILE_NAME(Raw File Name)=2DG_5.raw
SUBJECT_SAMPLE_FACTORS           	-	Saline_1	Sample source:Brain | Treatment:Saline	Genotype=WT; RAW_FILE_NAME(Raw File Name)=Saline_1.raw
SUBJECT_SAMPLE_FACTORS           	-	Saline_2	Sample source:Brain | Treatment:Saline	Genotype=WT; RAW_FILE_NAME(Raw File Name)=Saline_2.raw
SUBJECT_SAMPLE_FACTORS           	-	Saline_3	Sample source:Brain | Treatment:Saline	Genotype=WT; RAW_FILE_NAME(Raw File Name)=Saline_3.raw
SUBJECT_SAMPLE_FACTORS           	-	Saline_4	Sample source:Brain | Treatment:Saline	Genotype=WT; RAW_FILE_NAME(Raw File Name)=Saline_4.raw
SUBJECT_SAMPLE_FACTORS           	-	Saline_5	Sample source:Brain | Treatment:Saline	Genotype=WT; RAW_FILE_NAME(Raw File Name)=Saline_5.raw
#COLLECTION
CO:COLLECTION_SUMMARY            	Animals were euthanized by CO2 inhalation 16 hours following the final injection
CO:COLLECTION_SUMMARY            	and transcardially perfused with ice-cold PBS. Whole brains and spinal cords
CO:COLLECTION_SUMMARY            	were then excised, flash frozen in liquid N2, and stored at –80°C for
CO:COLLECTION_SUMMARY            	biochemical analysis.
CO:SAMPLE_TYPE                   	Brain
#TREATMENT
TR:TREATMENT_SUMMARY             	Mice were administered i.p. injections of saline (vehicle) or 4 g/kg 2DG (Cayman
TR:TREATMENT_SUMMARY             	Chemical) twice weekly for six weeks.
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	Metabolites from equal amounts of frontal cortex tissue were rapidly extracted
SP:SAMPLEPREP_SUMMARY            	in 80% ice-cold methanol. Extracted samples were vortexed twice, cleared by
SP:SAMPLEPREP_SUMMARY            	centrifugation at 14,000 x g for 20 minutes at 4°C, and stored at -80°C.
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_TYPE           	HILIC
CH:INSTRUMENT_NAME               	Thermo Vanquish
CH:COLUMN_NAME                   	Merck SeQuant ZIC-pHILIC (150 x 2.1mm,5um)
CH:SOLVENT_A                     	100% acetonitrile
CH:SOLVENT_B                     	100% water; 0.1% ammonium hydroxide; 20 mM ammonium acetate
CH:FLOW_GRADIENT                 	85% to 30% A in 20 min followed by a wash with 30% A and re-equilibration at 85%
CH:FLOW_GRADIENT                 	A
CH:FLOW_RATE                     	150 μL/min
CH:COLUMN_TEMPERATURE            	30
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:INSTRUMENT_NAME               	Thermo Q Exactive Orbitrap
MS:INSTRUMENT_TYPE               	Orbitrap
MS:MS_TYPE                       	ESI
MS:ION_MODE                      	UNSPECIFIED
MS:MS_COMMENTS                   	1. A Sequant ZIC-pHILIC column (2.1 mm i.d. × 150 mm, particle size of 5 µm,
MS:MS_COMMENTS                   	Millipore Sigma) was used for separation of metabolites. A 2.1 × 20 mm
MS:MS_COMMENTS                   	guard column with the same packing material was used for protection of the
MS:MS_COMMENTS                   	analytical column. Flow rate was set at 150 μL/min. Buffers consisted of 100%
MS:MS_COMMENTS                   	acetonitrile for mobile phase A, and 100% acetonitrile for mobile phase B. The
MS:MS_COMMENTS                   	chromatographic gradient ran from 85% to 30% A in 20 min followed by a wash with
MS:MS_COMMENTS                   	30% A and re-equilibration at 85% A. Column temperature was 30 C.
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	peak intensity
MS_METABOLITE_DATA_START
Samples	2DG_1	2DG_2	2DG_3	2DG_4	2DG_5	Saline_1	Saline_2	Saline_3	Saline_4	Saline_5
Factors	Sample source:Brain | Treatment:2DG	Sample source:Brain | Treatment:2DG	Sample source:Brain | Treatment:2DG	Sample source:Brain | Treatment:2DG	Sample source:Brain | Treatment:2DG	Sample source:Brain | Treatment:Saline	Sample source:Brain | Treatment:Saline	Sample source:Brain | Treatment:Saline	Sample source:Brain | Treatment:Saline	Sample source:Brain | Treatment:Saline
1-Methyladenosine	18071.72	29601.59	20265.86	20179.12	25176.21	20435.63	15805.12	26556.56	18352.03	27356.23
1-Methylnicotinamide	0	0	0	0	0	0	0	0	0	0
2-Hydroxycaproic acid	252036.5	336503.3	150708.8	182674.3	208359	342401.1	268423	231255.7	224091.6	303093.6
2-Hydroxyvaleric acid	2022956	1894132	1561093	1544935	3276415	3049344	2903548	3769964	2819770	2507179
3-Hydroxymethylglutaric acid	13556870	15763370	14454340	13115170	15221390	17466840	15363070	17481170	16075470	15261380
3-Indolepropionic acid	5807.522	17724.86	7704.766	8368.431	0	5648.745	8815.446	5694.466	6909.297	10304.33
3-Methylhistidine	12789620	9603358	9999853	8921684	8885028	16566540	12191780	16826830	10785260	13711690
3-Phosphoglyceric acid	620132.8	116324.7	422951.6	219568.2	458680.8	344162.8	206785.6	163721.6	172609.3	176084.9
4-Acetamidobutanoic acid	46045.81	43092.77	32575.34	39037.89	46626.91	39254.08	29085.13	46967.66	35428.63	32975.09
4-Guanidinobutanoic acid	25369180	35409220	30266640	28637260	25523500	34845760	32768170	19450590	33898070	34336890
4-Hydroxyproline	686297.9	785089.4	760941.4	370256.6	1042048	582524.2	590611.4	754577.1	640397.9	684553.6
4-Pyridoxic acid	40150.09	34054.97	20591.15	20710.53	33073.89	27534.29	32278.24	56385.55	24461.68	32769.61
4-Trimethylammoniobutanoic acid	44740840	16544860	24587280	20609160	39557420	22627920	19744900	46942940	15877420	18876510
5-Thymidylic acid	21217.02	0	0	0	0	0	0	20952.56	13723.12	0
6-Phosphogluconic acid	131992.5	131688.5	175743.7	165336.5	145896	189156.5	157567.1	107400.6	109946	137909.7
6-Phosphonoglucono-D-lactone	0	0	0	0	0	0	0	0	0	0
Acetyl-CoA	48207.97	48103.22	43729.89	45862.57	0	49953.14	45896.35	70377.66	42575.23	48469.41
Acetylcholine	30827770	10730870	8887630	9589687	14276310	23476840	13938970	31426450	11610480	11394450
Acetylcysteine	17751.24	9495.161	11938.73	8304.947	15173.49	7589.546	7026.146	14813.04	9404.046	9958.996
Adenine	57532370	78896990	48441640	51670050	66133490	72162600	72289640	80030930	73680770	77598780
Adenosine	510359200	569644700	378821000	362377200	600005100	420762400	415815200	770467500	471018300	476921600
Adenosine monophosphate	293154700	166545300	251022600	234724100	243260000	339932600	295190100	286926300	238276700	231522900
Adenosine triphosphate	55298.82	42226.78	58668.57	44131.63	64070.81	39622.98	45921.45	41131.29	31888.87	25967.82
ADP	1741428	541010.4	1250016	1025581	1670941	957723.4	1335735	886248.4	725768.8	841852.4
ADP-glucose	48651.97	57930.48	50349.39	52831.91	47750.59	89235.5	70518.15	73597.64	62812.55	62514.85
AICAR	265721.9	268141.1	252398.9	227734.9	294959.6	156866.6	163426.2	140513	125417.4	114242.2
Allantoin	564283.9	468667.9	364734.9	295323.6	543052.2	590014.9	537383.6	767742.6	486362.4	514008.1
Aminoadipic acid	1927212	2144710	2343838	1189015	2065791	2434013	2130197	1831133	1602844	1604167
Anserine	898437.7	719937.8	911614.5	990996.8	744031.3	1312312	801825.2	1242324	1102723	1168963
Argininosuccinic acid	848237.1	1336935	969789.8	859067.5	984727.5	894632	808320.9	939220.3	1006648	870770.3
Asymmetric dimethylarginine	4019863	3466609	2902151	4300072	3969144	4895214	4107970	4765254	3499095	4228862
Betaine	145072900	190533200	179342200	130802300	150686100	172759600	169059300	136329800	160977300	178806700
Butyrylcarnitine	26648530	18788020	19506820	35396130	21041330	28525710	33811250	19440730	22058050	23480590
Caprylic acid	1332729	1554668	1189772	1227729	1232416	1514423	1280417	1086439	1387895	1305085
Carnosine	140248600	145589600	127975500	130758100	159177600	155700300	136089700	233230400	133327400	147243900
CDP	17262.23	0	0	0	17467.67	0	0	0	0	0
CDP-Ethanolamine	2994532	1807672	1777802	1649207	2560438	2250865	1906025	3020473	1729336	1761456
Choline	28128390	59231190	44411680	35941120	38339280	45109910	32944530	42595220	53113650	42003240
cis-Aconitic acid	2213871	5405462	3586681	4108968	2541130	4870676	3306326	5602864	3980751	3712438
Citicoline	9066455	7897352	6801960	7131539	8017035	9256754	8831307	9786534	6930339	9249086
Citric acid	10026030	21837030	21909960	19151100	12632860	20389100	18771260	28591090	17225750	15299200
Citrulline	7329839	16771450	15785440	17048920	8420502	17723310	18837290	11471360	19635650	16579700
Coenzyme A	0	0	0	0	0	0	0	95911.18	93145.95	0
Creatine	1833928000	2151483000	2019593000	2012936000	1746102000	2323133000	2112693000	1835404000	1965508000	2035944000
Creatinine	50762710	61545550	50134150	60339260	52575520	66797980	53017040	48757900	49998500	51273970
Cyclic AMP	277023	114447	179289.9	131296.6	198919.6	224148.8	161820.3	243043.7	162981.6	134656.1
Cytidine	8217764	2048669	4917061	4313228	8570116	5265363	2637897	9639603	1959524	2700455
Cytidine monophosphate	3923832	3075407	2989602	2621002	3535552	3987320	2648752	5139000	2803018	2570240
Cytidine triphosphate	0	0	0	0	0	0	0	0	0	0
Cytosine	492460.3	293817.5	403379.1	527191.9	701120.7	432444.1	227370.5	649479.6	210207.9	272263.1
D-2-Hydroxyglutaric acid	7191603	6806436	7724898	6713837	7715719	7276678	6662210	7214574	7221464	6159315
D-Erythrose 4-phosphate	34583.16	245135	218971.3	466760.2	43650.89	47358.3	31110.71	57304.45	63008.14	47446.38
D-Fructose	134635.6	189447.7	259961.1	223273.5	127770.9	125348.7	103149.6	71718.41	125209.4	151029.8
D-Glucose	250109.7	764354.6	714518.9	699119	201025.7	505267.5	432344.7	193416.3	526502.9	597121
D-Glucuronic acid	0	0	0	0	0	0	0	0	0	0
D-Glyceraldehyde 3-phosphate	223782	1764489	731308.9	906232.9	217110.1	2010465	521459.5	314252.4	1078847	583956.6
D-Ribose	20054.67	84090.38	34627.89	43566.63	42341.71	54637.99	31547.21	48651.39	50362.68	46458.09
D-Ribose 5-phosphate	1393603	5593067	3919944	4240625	1858809	3399142	1903590	2528462	3188505	2665695
D-Ribulose	9483.203	9138.344	9471.749	7985.983	13613.09	0	5078.576	7218.322	7339.012	7355.748
D-Ribulose 5-phosphate	4658601	8488487	6325812	6625711	7113898	6367228	6532743	6971767	6518988	7116371
D-Sedoheptulose 7-phosphate	1104049	5169120	2998202	4612077	1447989	2516497	2180161	2663040	3026538	2974881
dCDP	0	0	0	0	0	0	0	0	0	0
dCMP	96914.08	0	0	0	126491.6	72890.52	0	88209.56	50287.6	52400.34
dCTP	0	0	0	0	0	0	0	0	0	0
Deoxyadenosine	153094.6	114441.6	184214.7	144851.7	230452.8	135148.1	86496.03	235013.3	100267.8	115570
Deoxyadenosine monophosphate	96305.14	78001.07	72692.16	61290.59	112393.4	122853.6	89957.7	131256.7	85203.15	84493.06
Deoxyadenosine triphosphate	0	0	0	0	0	0	0	0	0	0
Deoxycytidine	119932.2	69858.7	85630.84	130680.8	168254.2	88129.02	41421.22	169985.1	39148.78	62967.5
Deoxyinosine	14943.68	35460.38	18412.25	24016.49	30338.6	20728.36	19289.49	28597.35	18580.38	21904.73
Deoxyribose 5-phosphate	10633.23	14462.94	11770.79	14751.59	15482.85	18280.42	0	19039.02	15805.95	12488.19
Deoxyuridine	558577.4	814494.6	525856.7	588276	735457.6	565671.2	542528.4	766922.4	619638.6	689229.8
FAD	109993.2	173626.6	82758.87	141551	112609.4	107904.7	163523.5	183226.7	117925.1	116778.8
Flavin Mononucleotide	25809.75	36695.79	26567.7	41122.03	23690.31	62693.36	32145.1	26835.56	38300.45	31175.85
"Fructose 1,6-bisphosphate"	79428.46	200686.9	352079.8	450790.4	92072.3	166688.8	80880.02	35258.03	147746.2	105527.1
Fructose 6-phosphate	1774421	6066211	8259710	10881810	1804326	1769247	1495368	1132382	1930520	1895467
Fumaric acid	11249210	11641450	12071480	11150920	11896950	12150260	11485660	11654570	11844880	10913570
Galactonic acid	2572147	2372503	2132341	2102131	2805436	2632187	2625068	3320245	2154710	2473154
GDP-glucose	90535.55	85573.7	0	68783.34	0	0	105902.8	120816.5	0	0
Gluconic acid	2199095	2883238	2030624	1728505	1576775	4922440	3529050	3448132	3492978	3015898
Glucosamine	0	0	0	0	0	0	0	0	0	0
Glucosamine 6-phosphate	19895.12	59251.68	34858.99	52045.99	19477.96	0	0	0	11439.87	14762.5
Glucose 6-phosphate	3059331	14885770	13755350	24007980	3980102	4059717	2437110	1936476	3932645	3790421
Glutathione	164299700	76333340	137238200	120705200	132808200	87940340	108572800	216691500	102424600	135209300
Glycerol 3-phosphate	26184630	43164420	18150170	25744110	25032800	42404910	51261430	31084530	40483270	37934970
Glycerophosphocholine	394422700	347370500	341438600	256990700	368485100	455615600	418268500	361813100	368000200	354391400
Glycine	3198516	7304541	5712069	6225623	3835757	6456195	5830889	3485059	7323194	7181869
Guanidoacetic acid	35710.86	76919.63	58362.57	32101.81	43280.07	90652.94	94967.45	64143.41	93570.43	80199.2
Guanine	22013.8	756979.6	571526.9	604533.6	27430.43	483448.8	764368.9	42199.73	752154.1	981524.1
Guanosine	2436505	4563399	1949732	2403832	3685443	2871220	2765883	4861477	2857262	2806479
Guanosine diphosphate	321946.5	215110.8	229277.6	197128.6	297940.7	312500.9	397383.1	376711.2	206730.4	242842.3
Guanosine monophosphate	19083800	12534680	12810240	11827670	15585410	20760450	16168610	20217990	13464660	14611660
Guanosine triphosphate	0	0	0	0	0	0	0	0	0	0
Hexanoylcarnitine	510087.5	170820.2	295258.4	494415.3	372963.2	376565.7	390465.9	290666.2	249012.8	242017.4
Hippuric acid	84371.56	134606.4	51921.97	41003.96	74334.52	20457	9174.365	29934.04	14668.71	16019.04
Hypotaurine	168675.2	76549.97	141992.5	134918.2	167257.9	131456.8	119176.9	259342.5	105597.3	104559.6
Hypoxanthine	53215510	130455000	92819020	108529000	86797430	96021450	100917100	97776440	116058200	116248300
IDP	0	0	0	0	0	0	0	0	0	0
Imidazoleacetic acid	1071584	710556.3	530864	1031219	816376.9	851835.2	566866.2	725239.8	587041.4	490585.2
Indoxyl sulfate	275574.5	204074.3	52635.18	85993.23	68886.73	99807.7	113313.6	135910.2	55563.61	89933.13
Inosine	14192020	39707510	20528380	27536150	20652690	28510180	26745320	22841140	29010300	30633180
Inosinic acid	10160090	12773920	10577330	11747270	7902077	22332450	12312560	17243490	16556740	10537980
Isovalerylcarnitine	3351592	3494711	4146262	4996256	3658849	4436381	4015708	2643996	3930333	3762865
Kynurenic acid	0	0	0	0	0	0	0	0	0	0
L-Acetylcarnitine	485208800	576471300	627491600	614630100	470532300	646756100	642480700	467852100	592512600	621154000
L-Alanine	25007680	29212140	27048180	27881570	23571570	32136020	28459590	23653340	27190650	26853370
L-Arginine	60114290	86170920	65192550	70563740	75255760	67489440	81000020	67020880	73745180	77800730
L-Asparagine	18162320	17066960	15019840	14723200	20918040	20074030	17274640	21091820	15422110	16308660
L-Aspartic acid	141107900	175783700	164774900	165413500	155568400	187391500	178792900	161560300	175878000	182614800
L-Carnitine	333972800	415824600	398884400	425403600	345528400	462080400	470982800	329747000	503255300	525087900
L-Cystathionine	6181334	14829700	10590280	18516550	4670692	13199140	14187450	4530979	13334510	14968990
L-Cysteine	0	0	0	0	0	0	0	0	0	0
L-Cystine	0	0	0	0	0	0	0	0	0	0
L-Dihydroorotic acid	0	0	0	0	0	0	0	0	0	0
L-Glutamic acid	1171126000	1036242000	1104980000	1002696000	1163889000	1193687000	1096290000	1240860000	1090286000	1008334000
L-Glutamine	499613700	458360600	473904300	911605500	441539400	534085200	508338100	469651100	470303600	518410100
L-Glyceric acid	1545134	1547527	1407257	1512964	1790321	1629266	1259590	1475182	1269808	1240076
L-Histidine	48880620	75197430	55720250	63582890	53710000	70679860	69921620	66596160	68323180	73814020
L-Homoserine	13974850	14100290	14807880	10766010	15232200	15284830	14675370	16294680	12476300	13908120
L-Isoleucine	10239550	12144630	9347263	10717060	12960180	11478550	11539670	14291570	10210970	11978110
L-Kynurenine	28576.23	46042.32	34184.93	125234.7	45539.76	56531.85	33780.31	44559.27	35063.8	43771.95
L-Lactic acid	198889500	303803900	239622700	236323800	295438700	313925100	218441400	293174900	286630800	290927900
L-Leucine	25054010	30429620	22375220	26230160	34026400	26968480	27692200	32057840	23933440	32907760
L-Lysine	19511700	19420590	18003250	15512960	22055630	18446430	20026460	20648570	18740880	20473170
L-Methionine	16423710	14160470	15870890	15823760	17553480	15887360	14440890	16881990	14134590	12795470
L-Palmitoylcarnitine	54793.84	268921.7	18603.42	143956.8	444658.8	896803.3	137655.8	556331.3	58810.4	123159.4
L-Phenylalanine	27331800	31660210	25570030	50035660	33298970	28625300	26820340	30860120	25835580	28979330
L-Pipecolic acid	2724620	4688798	4389446	1600579	2947324	4356211	3989733	2963563	3985155	4193422
L-Proline	68271030	59578980	51282120	61680440	71410970	72071650	54259660	83211280	50576600	51439060
L-Serine	34305820	20371820	24224960	24599180	42576740	25037290	21508940	31725220	22023430	20103120
L-Threonine	10252770	12516080	12095310	9833918	10891850	12919280	12566160	11969030	12104340	12731200
L-Tryptophan	4442551	4972969	4228955	5721814	4695363	5272819	4502810	5071307	4645617	3789705
L-Tyrosine	9999107	9218775	8244602	14952220	10455130	11514560	10816740	12651490	8920834	8466862
L-Valine	18273970	17149250	15858160	16636660	21560880	19135970	17868430	22352720	17602200	17482810
Malic acid	84443200	86589660	95251260	83576870	89325870	91049120	85838140	86616720	88471350	82752640
Myoinositol	71507850	116903100	100772000	65642430	84874860	126661400	122199600	99834620	125234300	118437500
N-Acetyl-D-glucosamine	69181.91	52859.03	43295.21	41124.54	59769.54	25480.04	28121.9	40740.13	26436.42	28557.61
N-Acetyl-glucosamine 1-phosphate	597438.8	444465	382898	311723.6	682386.7	528606.5	391119.1	934853.3	353156.1	419429.3
N-Acetyl-L-alanine	482413.1	720468.3	458414	521606.7	624083.4	562172.1	512655.6	685275	543739.3	540854.6
N-Acetyl-L-aspartic acid	802369200	686457200	700385900	664248300	823075200	882483300	722661500	927217800	746456700	745158300
N-Acetyl-L-methionine	1178556	2231410	931591.8	985970.1	2053558	1046309	910694.7	2432937	1189912	1542334
N-Acetylasparagine	182604.2	216333.5	145093.3	286098.3	219083.2	563391.9	152606.2	234285.8	171803	131359
N-Acetylaspartylglutamic acid	20047000	113241000	76253140	104650300	20297790	113351600	107011500	20399550	104050400	94184090
N-Acetylglutamic acid	2134306	2326628	2022414	2228409	2301029	2695134	2646070	2607015	2360902	2440022
N-Acetylglutamine	543355.2	438078	544412.1	1507291	480796.2	574506.8	565452.9	494582.7	421792.4	475130.8
N-Acetylornithine	335052.4	270672.8	277713.8	332240.3	339471.2	365257.4	299814.6	427717.1	309466.2	324432.2
N-Acetylputrescine	0	0	0	0	0	0	0	0	0	0
N-acetyltryptophan	7467.399	11443.52	10140.05	20234.12	10269.99	10137.45	10598.37	7235.324	10592.28	9261.487
N-Formyl-L-methionine	0	0	0	0	0	0	0	0	0	0
N6-Acetyl-L-lysine	1156396	1115765	1211703	1055036	1244988	1346553	1103837	1413102	1053151	1296254
"N6,N6,N6-Trimethyl-L-lysine"	28493670	8855480	14109950	10964970	29578920	14342100	11652130	34716880	9478067	10778970
NAD	8244564	995987.6	2308486	485484.4	4224093	3577133	2896259	6366420	1277811	1282631
NADH	1509991	168464.5	468341.2	278388.7	644260.7	395827.1	520835.7	981453.4	220225.1	241978.8
NADP	38173.25	0	17435.97	0	26180.75	16006.29	24665.67	25818.66	0	14992.12
NADPH	0	0	0	0	0	0	0	0	0	0
Niacinamide	104933100	146834300	141850100	123265300	145615000	128668200	128230000	108009500	147685600	130638000
Nicotinamide riboside	578447.8	617992.1	499186.3	460538.8	565102.9	584747.5	746982.1	905022.5	563269.5	611337.4
Nicotinamide ribotide	368979.3	108137.1	167811.5	160198	308558.8	305511.6	318973.4	427561.5	159792.7	169286.6
Nicotinic acid	110714.6	136743.5	121223.1	135023.2	117596.1	136819.4	134607.1	146697.1	136949.4	120883.9
Nicotinic acid adenine dinucleotide	0	0	0	0	0	0	0	0	0	0
Nicotinic acid mononucleotide	0	0	0	0	0	0	0	0	0	0
O-Phosphoethanolamine	104188300	39182130	50681200	46250180	100588000	66069940	55066850	93913060	41008430	40828640
Ornithine	0	0	0	0	0	0	0	0	0	0
Orotic acid	685870.9	642551.5	662954.1	805975.2	814133.2	558520.9	598019.4	864942	588151.9	597032.1
Oxalacetic acid	0	0	0	0	0	0	0	0	0	0
Oxidized glutathione	43019020	37642270	31922020	28100600	39201570	57140880	45602780	34128260	37995920	40541780
Oxoglutaric acid	752072.1	402941.2	714907.2	518279.4	668160.2	1709290	543811.8	1603979	485907.3	428540.7
Palmitic acid	4040325	4956063	3818611	4240163	6590868	12192530	4106716	12971930	3515703	3700767
Pantothenic acid	23592810	39073830	32274740	43867970	24600230	33433020	35709090	29699470	34362310	43304320
Phosphocreatine	1512844	903270.2	680531.4	799486.7	584605.8	1934496	1186722	1682561	1176580	1099153
Phosphoenolpyruvic acid	96672.06	16353.23	41097.35	32119.83	78038.52	67605.19	37022.39	95052.18	24773.64	29923.59
Phosphorylcholine	463046400	327266700	400295600	413947100	482791800	473420900	421561600	548260500	356150800	393224800
Phosphoserine	30632.15	21823.99	27871.41	20770.74	42483.61	21170.28	19965.71	33177.61	23397.45	19628.6
Propionylcarnitine	12114170	19382400	14558500	12640900	12996360	29589480	29131320	16970190	20271520	26398620
Purine	0	20842.26	14709.57	25033.45	15478.2	6732.917	9238.563	8561.953	11031.73	10050.45
Pyridoxine	0	0	0	0	0	0	0	0	0	0
Pyroglutamic acid	9083174	16394620	12944100	21875160	11164020	11149900	9190057	12387660	13133910	13866550
Pyruvic acid	608428.6	564926.6	577122.5	575075.4	556909.2	701434.4	625423.7	619364.8	606822.4	580995.8
Riboflavin	64464.28	92790.17	48556.52	81277.62	83398.04	89883.01	88099.95	147591.7	55286.8	70361.93
S-Adenosylhomocysteine	3232633	3748679	3122260	2690293	3684940	3414546	2969820	4656133	2716471	2959100
S-Adenosylmethionine	3737208	4378089	3616028	4509134	3927514	4077517	5276703	3660138	3369053	3221664
"Sedoheptulose 1,7-bisphosphate"	12682	19912.21	22901.46	33604.29	16421.03	19752.67	9275.169	6328.041	8810.664	10431.56
Succinic acid	18363620	16544070	9071933	11855620	17622380	23723230	23775370	22407910	15146440	21011110
Succinyl-CoA	0	0	0	0	0	0	0	0	0	0
Taurine	189176400	131441800	147759000	137948600	191595600	163151900	142471300	204979200	139212800	142121100
Thiamine	922140.4	747482.4	631164.1	579685.5	892064.9	723324.6	784844.7	1039055	507134.1	696811.8
Thiamine monophosphate	701236.7	1637712	967881.7	1172770	1012379	1002887	1066737	931165	1387748	1238766
Thymidine	547238.8	897099.7	570041.9	672432.2	845890.1	472255	461171.1	643601.8	474996.6	550904.2
Thymidine 5'-triphosphate	0	0	0	0	0	0	0	0	0	0
Thymine	82562.97	124651.9	93549.48	114468.3	124063.1	76158.82	75138.4	95598.45	76460.96	88909.38
Uracil	3003195	3593269	2368585	2386399	4082146	2460131	2769332	5158349	2638088	2796553
Ureidopropionic acid	402354.9	583792.1	451617.7	528816.1	524864.2	574999.2	639525.6	468992.6	538051.2	708647.7
Ureidosuccinic acid	291800.1	104260	166784.6	143675.9	209500.2	114826.5	140302.4	197604	131488.8	95065.27
Uric acid	1588201	2470242	1519407	1719608	1679056	2557848	2819014	3509999	2289309	2537028
Uridine	23158180	31243110	26794530	28679470	28036620	26356070	27222640	29968550	27944810	28296540
Uridine 5'-diphosphate	38150.78	11567.2	20744.33	18178.56	39095.43	20421.05	15375.12	12740.65	12835.72	10849
Uridine 5'-monophosphate	6488815	4522133	4939597	4776241	5251102	7314132	5231483	5976845	5178765	6537770
Uridine diphosphate-N-acetylglucosamine	2358106	1891389	0	1595269	2203455	3095284	2529683	3555106	2382372	2278980
Uridine diphosphate glucose	2303555	1887415	1925247	2252701	1876842	2557450	2228902	2492264	1726329	1702319
Uridine diphosphate glucuronic acid	31603.82	26857.24	0	0	0	0	40438.81	0	0	20943.7
Uridine triphosphate	0	0	0	0	0	0	0	0	0	0
Urocanic acid	3023881	1840372	1436514	1409767	2665339	1787312	553826.4	1336565	1161095	1273898
Xanthine	9495254	13985650	8281733	9815354	14119270	9844726	9437991	18084230	10577490	11874360
Xanthosine	0	0	0	0	0	0	0	0	0	0
2DGP	34911160	33311060	32651360	30735370	33872620	254379.8	236313.5	233092	209570.3	217287.6
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	HMDB
1-Methyladenosine	HMDB0003331
1-Methylnicotinamide	HMDB0000699
2-Hydroxycaproic acid	HMDB0001624
2-Hydroxyvaleric acid	HMDB0001863
3-Hydroxymethylglutaric acid	HMDB0000355
3-Indolepropionic acid	HMDB0002302
3-Methylhistidine	HMDB0000479
3-Phosphoglyceric acid	HMDB0000807
4-Acetamidobutanoic acid	HMDB0003681
4-Guanidinobutanoic acid	HMDB0003464
4-Hydroxyproline	HMDB0000725
4-Pyridoxic acid	HMDB0000017
4-Trimethylammoniobutanoic acid	HMDB0001161
5-Thymidylic acid	HMDB0001227
6-Phosphogluconic acid	HMDB0001316
6-Phosphonoglucono-D-lactone	HMDB0001127
Acetyl-CoA	HMDB0001206
Acetylcholine	HMDB0000895
Acetylcysteine	HMDB0001890
Adenine	HMDB0000034
Adenosine	HMDB0000050
Adenosine monophosphate	HMDB0000045
Adenosine triphosphate	HMDB0000538
ADP	HMDB0001341
ADP-glucose	HMDB0006557
AICAR	HMDB0001517
Allantoin	HMDB0000462
Aminoadipic acid	HMDB0000510
Anserine	HMDB0000194
Argininosuccinic acid	HMDB0000052
Asymmetric dimethylarginine	HMDB0001539
Betaine	HMDB0000043
Butyrylcarnitine	HMDB0002013
Caprylic acid	HMDB0000482
Carnosine	HMDB0000033
CDP	HMDB0001546
CDP-Ethanolamine	HMDB0001564
Choline	HMDB0000097
cis-Aconitic acid	HMDB0000072
Citicoline	HMDB0001413
Citric acid	HMDB0000094
Citrulline	HMDB0000904
Coenzyme A	HMDB0001423
Creatine	HMDB0000064
Creatinine	HMDB0000562
Cyclic AMP	HMDB0000058
Cytidine	HMDB0000089
Cytidine monophosphate	HMDB0000095
Cytidine triphosphate	HMDB0000082
Cytosine	HMDB0000630
D-2-Hydroxyglutaric acid	HMDB0000606
D-Erythrose 4-phosphate	HMDB0001321
D-Fructose	HMDB0000660
D-Glucose	HMDB0000122
D-Glucuronic acid	HMDB0000127
D-Glyceraldehyde 3-phosphate	HMDB0001112
D-Ribose	HMDB0000283
D-Ribose 5-phosphate	HMDB0001548
D-Ribulose	HMDB0000621
D-Ribulose 5-phosphate	HMDB0000618
D-Sedoheptulose 7-phosphate	HMDB0001068
dCDP	HMDB0001245
dCMP	HMDB0001202
dCTP	HMDB0000998
Deoxyadenosine	HMDB0000101
Deoxyadenosine monophosphate	HMDB0000905
Deoxyadenosine triphosphate	HMDB0001532
Deoxycytidine	HMDB0000014
Deoxyinosine	HMDB0000071
Deoxyribose 5-phosphate	HMDB0001031
Deoxyuridine	HMDB0000012
FAD	HMDB0001248
Flavin Mononucleotide	HMDB0001520
"Fructose 1,6-bisphosphate"	HMDB0001058
Fructose 6-phosphate	HMDB0000124
Fumaric acid	HMDB0000134
Galactonic acid	HMDB0000565
GDP-glucose	HMDB0003351
Gluconic acid	HMDB0000625
Glucosamine	HMDB0001514
Glucosamine 6-phosphate	HMDB0001254
Glucose 6-phosphate	HMDB0001401
Glutathione	HMDB0000125
Glycerol 3-phosphate	HMDB0000126
Glycerophosphocholine	HMDB0000086
Glycine	HMDB0000123
Guanidoacetic acid	HMDB0000128
Guanine	HMDB0000132
Guanosine	HMDB0000133
Guanosine diphosphate	HMDB0001201
Guanosine monophosphate	HMDB0001397
Guanosine triphosphate	HMDB0001273
Hexanoylcarnitine	HMDB0000705
Hippuric acid	HMDB0000714
Hypotaurine	HMDB0000965
Hypoxanthine	HMDB0000157
IDP	HMDB0003335
Imidazoleacetic acid	HMDB0002024
Indoxyl sulfate	HMDB0000682
Inosine	HMDB0000195
Inosinic acid	HMDB0000175
Isovalerylcarnitine	HMDB0000688
Kynurenic acid	HMDB0000715
L-Acetylcarnitine	HMDB0000201
L-Alanine	HMDB0000161
L-Arginine	HMDB0000517
L-Asparagine	HMDB0000168
L-Aspartic acid	HMDB0000191
L-Carnitine	HMDB0000062
L-Cystathionine	HMDB0000099
L-Cysteine	HMDB0000574
L-Cystine	HMDB0000192
L-Dihydroorotic acid	HMDB0003349
L-Glutamic acid	HMDB0000148
L-Glutamine	HMDB0000641
L-Glyceric acid	HMDB0006372
L-Histidine	HMDB0000177
L-Homoserine	HMDB0000719
L-Isoleucine	HMDB0000172
L-Kynurenine	HMDB0000684
L-Lactic acid	HMDB0000190
L-Leucine	HMDB0000687
L-Lysine	HMDB0000182
L-Methionine	HMDB0000696
L-Palmitoylcarnitine	HMDB0000222
L-Phenylalanine	HMDB0000159
L-Pipecolic acid	HMDB0000716
L-Proline	HMDB0000162
L-Serine	HMDB0000187
L-Threonine	HMDB0000167
L-Tryptophan	HMDB0000929
L-Tyrosine	HMDB0000158
L-Valine	HMDB0000883
Malic acid	HMDB0000744
Myoinositol	HMDB0000211
N-Acetyl-D-glucosamine	HMDB0000215
N-Acetyl-glucosamine 1-phosphate	HMDB0001367
N-Acetyl-L-alanine	HMDB0000766
N-Acetyl-L-aspartic acid	HMDB0000812
N-Acetyl-L-methionine	HMDB0011745
N-Acetylasparagine	HMDB0006028
N-Acetylaspartylglutamic acid	HMDB0001067
N-Acetylglutamic acid	HMDB0001138
N-Acetylglutamine	HMDB0006029
N-Acetylornithine	HMDB0003357
N-Acetylputrescine	HMDB0002064
N-acetyltryptophan	HMDB0013713
N-Formyl-L-methionine	HMDB0001015
N6-Acetyl-L-lysine	HMDB0000206
"N6,N6,N6-Trimethyl-L-lysine"	HMDB0001325
NAD	HMDB0000902
NADH	HMDB0001487
NADP	HMDB0000217
NADPH	HMDB0000221
Niacinamide	HMDB0001406
Nicotinamide riboside	HMDB0000855
Nicotinamide ribotide	HMDB0000229
Nicotinic acid	HMDB0001488
Nicotinic acid adenine dinucleotide	HMDB0001179
Nicotinic acid mononucleotide	HMDB0001132
O-Phosphoethanolamine	HMDB0000224
Ornithine	HMDB0000214
Orotic acid	HMDB0000226
Oxalacetic acid	HMDB0000223
Oxidized glutathione	HMDB0003337
Oxoglutaric acid	HMDB0000208
Palmitic acid	HMDB0000220
Pantothenic acid	HMDB0000210
Phosphocreatine	HMDB0001511
Phosphoenolpyruvic acid	HMDB0000263
Phosphorylcholine	HMDB0001565
Phosphoserine	HMDB0000272
Propionylcarnitine	HMDB0000824
Purine	HMDB0001366
Pyridoxine	HMDB0000239
Pyroglutamic acid	HMDB0000267
Pyruvic acid	HMDB0000243
Riboflavin	HMDB0000244
S-Adenosylhomocysteine	HMDB0000939
S-Adenosylmethionine	HMDB0001185
"Sedoheptulose 1,7-bisphosphate"	HMDB0060274
Succinic acid	HMDB0000254
Succinyl-CoA	HMDB0001022
Taurine	HMDB0000251
Thiamine	HMDB0000235
Thiamine monophosphate	HMDB0002666
Thymidine	HMDB0000273
Thymidine 5'-triphosphate	HMDB0001342
Thymine	HMDB0000262
Uracil	HMDB0000300
Ureidopropionic acid	HMDB0000026
Ureidosuccinic acid	HMDB0000828
Uric acid	HMDB0000289
Uridine	HMDB0000296
Uridine 5'-diphosphate	HMDB0000295
Uridine 5'-monophosphate	HMDB0000288
Uridine diphosphate-N-acetylglucosamine	HMDB0000290
Uridine diphosphate glucose	HMDB0000286
Uridine diphosphate glucuronic acid	HMDB0000935
Uridine triphosphate	HMDB0000285
Urocanic acid	HMDB0000301
Xanthine	HMDB0000292
Xanthosine	HMDB0000299
2DGP
METABOLITES_END
#END