#METABOLOMICS WORKBENCH juliehaines_20220622_115233 DATATRACK_ID:3314 STUDY_ID:ST002213 ANALYSIS_ID:AN003621 PROJECT_ID:PR001414
VERSION             	1
CREATED_ON             	July 8, 2022, 5:01 pm
#PROJECT
PR:PROJECT_TITLE                 	Metabolic changes in Alzheimer patient-derived induced neurons and the effects
PR:PROJECT_TITLE                 	of PKM2 modulation and hypoxia on their metabolic landscape
PR:PROJECT_SUMMARY               	We have obtained fibroblast cultures from old adult human non-demented control
PR:PROJECT_SUMMARY               	donors and Alzheimer patients (AD). The fibroblasts were reprogrammed into
PR:PROJECT_SUMMARY               	directly induced neurons (iNs) to serve as an adult-like and age-equivalent
PR:PROJECT_SUMMARY               	model for aging and neurodegeneration. Metabolomic landscape and glucose flux in
PR:PROJECT_SUMMARY               	control versus AD were assessed. Additionally, their response to PKM2 modulation
PR:PROJECT_SUMMARY               	(shikonin 10 µM or PKM2 overexpression) and hypoxia (CoDo treatment) were
PR:PROJECT_SUMMARY               	assessed.
PR:INSTITUTE                     	University of Colorado Denver
PR:LABORATORY                    	Lab of Angelo D'Alessandro in collaboration with lab of Jerome Mertens (Univ of
PR:LABORATORY                    	Innsbruck)
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                   	Metabolic changes in Alzheimer patient-derived induced neurons and the effects
ST:STUDY_TITLE                   	of PKM2 modulation and hypoxia on their metabolic landscape
ST:STUDY_SUMMARY                 	We have obtained fibroblast cultures from old adult human non-demented control
ST:STUDY_SUMMARY                 	donors and Alzheimer patients (AD). The fibroblasts were reprogrammed into
ST:STUDY_SUMMARY                 	directly induced neurons (iNs) to serve as an adult-like and age-equivalent
ST:STUDY_SUMMARY                 	model for aging and neurodegeneration. Metabolomic landscape and glucose flux in
ST:STUDY_SUMMARY                 	control versus AD were assessed. Additionally, their response to PKM2 modulation
ST:STUDY_SUMMARY                 	(shikonin 10 µM or PKM2 overexpression) and hypoxia (CoDo treatment) were
ST:STUDY_SUMMARY                 	assessed.
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                  	Human
SU:SUBJECT_SPECIES               	Homo sapiens
SU:TAXONOMY_ID                   	9606
SU:AGE_OR_AGE_RANGE              	50-90 yrs
#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           	-	Control3	Condition:Non-demented control	RAW_FILE_NAME=3
SUBJECT_SAMPLE_FACTORS           	-	AD6	Condition:Alzheimer patient	RAW_FILE_NAME=6
SUBJECT_SAMPLE_FACTORS           	-	AD7	Condition:Alzheimer patient	RAW_FILE_NAME=7
SUBJECT_SAMPLE_FACTORS           	-	Control9	Condition:Non-demented control	RAW_FILE_NAME=9
SUBJECT_SAMPLE_FACTORS           	-	AD2	Condition:Alzheimer patient	RAW_FILE_NAME=10
SUBJECT_SAMPLE_FACTORS           	-	Control2	Condition:Non-demented control	RAW_FILE_NAME=11
SUBJECT_SAMPLE_FACTORS           	-	AD8	Condition:Alzheimer patient	RAW_FILE_NAME=14
SUBJECT_SAMPLE_FACTORS           	-	Control10	Condition:Non-demented control	RAW_FILE_NAME=15
SUBJECT_SAMPLE_FACTORS           	-	AD11	Condition:Alzheimer patient	RAW_FILE_NAME=17
SUBJECT_SAMPLE_FACTORS           	-	Control11	Condition:Non-demented control	RAW_FILE_NAME=18
SUBJECT_SAMPLE_FACTORS           	-	AD10	Condition:Alzheimer patient	RAW_FILE_NAME=19
SUBJECT_SAMPLE_FACTORS           	-	AD1	Condition:Alzheimer patient	RAW_FILE_NAME=20
SUBJECT_SAMPLE_FACTORS           	-	Control7	Condition:Non-demented control	RAW_FILE_NAME=22
SUBJECT_SAMPLE_FACTORS           	-	AD3	Condition:Alzheimer patient	RAW_FILE_NAME=23
SUBJECT_SAMPLE_FACTORS           	-	Control8	Condition:Non-demented control	RAW_FILE_NAME=24
SUBJECT_SAMPLE_FACTORS           	-	AD5	Condition:Alzheimer patient	RAW_FILE_NAME=25
SUBJECT_SAMPLE_FACTORS           	-	Control6	Condition:Non-demented control	RAW_FILE_NAME=27
SUBJECT_SAMPLE_FACTORS           	-	Control4	Condition:Non-demented control	RAW_FILE_NAME=29
SUBJECT_SAMPLE_FACTORS           	-	Control8 media	Condition:non-demented control	RAW_FILE_NAME=31
SUBJECT_SAMPLE_FACTORS           	-	Control6 media	Condition:non-demented control	RAW_FILE_NAME=32
SUBJECT_SAMPLE_FACTORS           	-	AD6 media	Condition:Alzheimer patient	RAW_FILE_NAME=33
SUBJECT_SAMPLE_FACTORS           	-	AD3 media	Condition:Alzheimer patient	RAW_FILE_NAME=35
SUBJECT_SAMPLE_FACTORS           	-	AD7 media	Condition:Alzheimer patient	RAW_FILE_NAME=36
SUBJECT_SAMPLE_FACTORS           	-	Control9 media	Condition:non-demented control	RAW_FILE_NAME=38
SUBJECT_SAMPLE_FACTORS           	-	AD2 media	Condition:Alzheimer patient	RAW_FILE_NAME=39
SUBJECT_SAMPLE_FACTORS           	-	Control2 media	Condition:non-demented control	RAW_FILE_NAME=40
SUBJECT_SAMPLE_FACTORS           	-	Control10 media	Condition:non-demented control	RAW_FILE_NAME=44
SUBJECT_SAMPLE_FACTORS           	-	AD11 media	Condition:Alzheimer patient	RAW_FILE_NAME=46
SUBJECT_SAMPLE_FACTORS           	-	Control11 media	Condition:non-demented control	RAW_FILE_NAME=47
SUBJECT_SAMPLE_FACTORS           	-	AD10 media	Condition:Alzheimer patient	RAW_FILE_NAME=48
SUBJECT_SAMPLE_FACTORS           	-	AD1 media	Condition:Alzheimer patient	RAW_FILE_NAME=49
SUBJECT_SAMPLE_FACTORS           	-	Control7 media	Condition:non-demented control	RAW_FILE_NAME=51
SUBJECT_SAMPLE_FACTORS           	-	AD5 media	Condition:Alzheimer patient	RAW_FILE_NAME=52
SUBJECT_SAMPLE_FACTORS           	-	AD8 media	Condition:Alzheimer patient	RAW_FILE_NAME=53
SUBJECT_SAMPLE_FACTORS           	-	Control4 media	Condition:non-demented control	RAW_FILE_NAME=55
SUBJECT_SAMPLE_FACTORS           	-	Control3 media	Condition:non-demented control	RAW_FILE_NAME=56
#COLLECTION
CO:COLLECTION_SUMMARY            	For Metabolome, iNs were flow cytometry-isolated 21 days of conversion. iNs were
CO:COLLECTION_SUMMARY            	sorted based on the expression of the PSA-NCAM surface markers using PSA-NCAM-PE
CO:COLLECTION_SUMMARY            	(Miltenyi) and re-plated on Geltrex-coated wells. The following day, iNs were
CO:COLLECTION_SUMMARY            	treated with 2.5 mM DGlucose-C13 for 6 hours and harvested using Tryple.
CO:COLLECTION_SUMMARY            	Supernatant and cell pellets were shock frozen in liquid nitrogen.
CO:SAMPLE_TYPE                   	Biopsy
#TREATMENT
TR:TREATMENT_SUMMARY             	After two weeks of conversion, cells were treated for 10 days with shikonin (10
TR:TREATMENT_SUMMARY             	µM, ChemCruz) before FACS sorting. Control iNs were FACS-sorted and plated on
TR:TREATMENT_SUMMARY             	Geltrex-coated wells before transduction with pLVXTP-EGFP-PKM2 or pLVXTP-EGFP.
TR:TREATMENT_SUMMARY             	Around 60 % of all neurons were successfully transduced. Five days after
TR:TREATMENT_SUMMARY             	transduction, iNs were harvested for MS-analysis. Alternatively, cells were
TR:TREATMENT_SUMMARY             	treated with CoDo for 6 hours before harvest.
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	Metabolites from frozen cell pellets were extracted at 1e6 cells/mL in cold
SP:SAMPLEPREP_SUMMARY            	5:3:2 MeOH:acetonitrile:water. Metabolites from supernatant samples (10 uL) were
SP:SAMPLEPREP_SUMMARY            	extracted with 240 uL of the above extraction solution. Samples were vortexed 30
SP:SAMPLEPREP_SUMMARY            	min at 4 degrees C then supernatants clarified by centrifugation (10 min, 10,000
SP:SAMPLEPREP_SUMMARY            	g, 4 degrees C).
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_SUMMARY        	Positive C18 media
CH:CHROMATOGRAPHY_TYPE           	Reversed phase
CH:INSTRUMENT_NAME               	Thermo Vanquish
CH:COLUMN_NAME                   	Phenomenex kinetex C18 2.1 x 150 mm, 1.7 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                      	POSITIVE
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	Control7	Control4	Control10	Control2	Control3	Control6	Control8	Control9	Control11	AD3	AD5	AD2	AD7	AD8	AD1	AD10	AD11
Factors	Condition:Non-demented control	Condition:Non-demented control	Condition:Non-demented control	Condition:Non-demented control	Condition:Non-demented control	Condition:Non-demented control	Condition:Non-demented control	Condition:Non-demented control	Condition:Non-demented control	Condition:Alzheimer patient	Condition:Alzheimer patient	Condition:Alzheimer patient	Condition:Alzheimer patient	Condition:Alzheimer patient	Condition:Alzheimer patient	Condition:Alzheimer patient	Condition:Alzheimer patient
L-alanine	11067240.00	33435360.00	21989060.00	6263340.00	5166949.00	5746696.00	5051252.00	11398000.00	6848624.00	7535902.00	27271120.00	80286940.00	10906590.00	27620400.00	17525960.00	2073174.00	33785790.00
L-arginine	20604240.00	57260580.00	54372370.00	62808140.00	22678520.00	21548290.00	22117880.00	39015360.00	41504680.00	20907670.00	63300420.00	119319500.00	33752350.00	50534340.00	60755410.00	27004430.00	76079360.00
L-asparagine	2443395.00	2775507.00	1537712.00	663298.20	3765668.00	4078973.00	3395671.00	1207326.00	376916.00	3626283.00	1699834.00	5807316.00	744345.90	2148026.00	1398075.00	226334.40	2400062.00
L-aspartate	42131.33	9167315.00	3201085.00	3699031.00	56750.23	22141.48	3506.67	2383060.00	2589830.00	74626.03	9452792.00	29048930.00	1760470.00	20982860.00	8793929.00	1113929.00	6273762.00
L-cysteine	6528.72	5543159.00	4474774.00	116419.20	4416.04	4915.84	6665.44	2939729.00	2479997.00	12423.52	5266704.00	9480565.00	2590161.00	5710690.00	6209630.00	323503.10	7397234.00
L-glutamate	267744.40	26451440.00	33295410.00	11090500.00	123579.50	120726.50	233951.10	16197450.00	8810221.00	109727.90	48276910.00	171990300.00	21330290.00	52041680.00	50550140.00	6054064.00	44575990.00
L-glutamine	4802468.00	9826147.00	8486487.00	1808415.00	2165186.00	2840535.00	2210332.00	4206184.00	3154242.00	2921725.00	11615440.00	42684570.00	2661678.00	9791657.00	7621880.00	786058.20	13348720.00
glycine	4889444.00	3573123.00	3722565.00	3586645.00	4178807.00	4312684.00	3839334.00	3431139.00	3584580.00	4327570.00	3774387.00	3606033.00	3492621.00	3758084.00	3692973.00	3663810.00	3506564.00
L-histidine	7961424.00	6197898.00	4799587.00	3671274.00	7449890.00	7466832.00	8547531.00	3350432.00	2006362.00	8301296.00	6652114.00	13457550.00	2756384.00	4906688.00	3729249.00	807432.70	8579070.00
L-leucine	523122400.00	395299300.00	293315000.00	127044100.00	533906900.00	505505400.00	532142700.00	265179300.00	92752180.00	474172300.00	367913100.00	718866400.00	197816400.00	242978400.00	181856800.00	31052880.00	509572100.00
L-lysine	34965550.00	40394800.00	40958210.00	14461810.00	33772380.00	40228100.00	37618240.00	27882130.00	13293400.00	43680680.00	43365720.00	65667480.00	17296240.00	40117480.00	29130430.00	7602214.00	58497170.00
L-methionine	33903120.00	74978100.00	79442190.00	28613650.00	34844350.00	32407800.00	35282940.00	43659230.00	33099020.00	30768020.00	91685590.00	135886100.00	46314740.00	67642650.00	50379770.00	9842585.00	100541000.00
L-phenylalanine	33034890.00	51109150.00	60927020.00	28904740.00	41300640.00	38813720.00	36873810.00	37494940.00	20481550.00	40571780.00	46426370.00	112696200.00	53507270.00	58252970.00	21725450.00	5924664.00	86707350.00
L-proline	27091210.00	343491400.00	328729300.00	132418700.00	26225500.00	27377670.00	27521100.00	230505800.00	122677200.00	28135380.00	344530000.00	559986800.00	229655300.00	282976500.00	198912800.00	51076850.00	472047200.00
L-serine	25302.73	9619714.00	4066212.00	939697.80	93601.78	125050.10	19999.82	2410022.00	1607401.00	50432.46	6200294.00	28930170.00	1969203.00	9630125.00	6697024.00	413884.40	7912938.00
L-threonine	9968365.00	20920180.00	13037580.00	3276011.00	8922340.00	9253503.00	9227003.00	5983796.00	3679138.00	8373728.00	18297060.00	63632210.00	6108208.00	17887980.00	11424950.00	1160209.00	20208250.00
L-tryptophan	92635040.00	80414810.00	116091400.00	58863090.00	100965100.00	110507300.00	100911300.00	89069590.00	23396530.00	103338600.00	90951010.00	110748800.00	107781100.00	79118900.00	44547430.00	12871320.00	151046700.00
L-tyrosine	25292250.00	63860650.00	57846600.00	20098980.00	28100310.00	22705270.00	26563460.00	31912330.00	22437400.00	24229940.00	74640320.00	148330300.00	39552930.00	60206800.00	39677550.00	5971874.00	83093710.00
L-valine	162018200.00	222888400.00	193209800.00	56432310.00	187414300.00	185143600.00	182344900.00	126371300.00	57488410.00	178411700.00	188477100.00	323293300.00	150979200.00	181623700.00	86531300.00	19595420.00	253675300.00
L-cystine	27196.51	146846.80	83213.56	221006.10	41418.26	28741.95	23591.82	22986.48	73285.96	88134.16	178882.60	672302.60	35576.25	443510.80	84361.58	49036.36	231259.20
Adenosine	128912.80	25400.87	31692.81	31526.58	117771.20	145364.90	100293.70	35818.02	37524.64	156677.70	31650.84	15816.92	28734.16	0.00	34263.72	32132.80	32100.63
CMP	0.00	111009.30	256824.00	198066.30	0.00	0.00	0.00	140257.70	123277.40	0.00	470300.40	392093.50	127874.00	295943.60	201682.90	41279.00	361976.90
Hypoxanthine	272942.70	58582830.00	25160990.00	18077420.00	200530.50	173538.00	247584.30	14002540.00	12313810.00	114809.00	57173630.00	161108700.00	27138110.00	18032500.00	24114030.00	3351130.00	59432560.00
3',5'-Cyclic AMP	495290.20	455491.00	22777.29	82416.12	2062366.00	1738641.00	1810846.00	58590.52	105009.20	1224924.00	19791.22	87721.91	23376.52	31871.38	78144.70	68448.91	35282.83
4-Pyridoxate	15493.12	63823.42	108846.50	22345.97	42851.86	32868.53	22428.37	99502.60	44646.33	29188.08	102455.80	110701.30	64845.89	408442.90	68062.59	70306.45	391687.20
Nicotinamide	11693710.00	14220110.00	5294748.00	1408069.00	10311100.00	10470270.00	10037690.00	3113059.00	2499918.00	9061883.00	40678760.00	31895190.00	2081793.00	11096360.00	5477020.00	1418457.00	13432390.00
NAD+	0.00	103822.10	88766.21	74681.52	0.00	0.00	0.00	38561.10	56676.05	0.00	0.00	468784.20	18352.25	501002.40	223667.20	23804.37	187052.50
D-Glucono-1-5-lactone 6-phosphate	53299.01	606958.10	516515.20	591850.90	11029.98	67317.43	29466.65	267759.30	471189.50	24947.30	624595.20	2030115.00	271715.90	2239739.00	442739.50	178618.00	1861142.00
Cys-Gly	7219.81	738326.60	862883.30	529409.60	5811.01	4518.54	11643.95	726855.90	482700.80	5871.09	1652470.00	4094067.00	815464.80	2347708.00	1602414.00	180400.80	1757985.00
gamma-L-Glutamyl-L-cysteine	263561.10	331850.40	700110.20	760233.50	130236.50	118267.50	122934.50	1036505.00	515859.00	120320.60	1736004.00	5277622.00	931623.70	1303036.00	499111.20	186875.60	1727853.00
gamma-Glutamyl-Se-methylselenocysteine	231863.10	150139.20	176380.50	66582.91	302130.50	291958.20	359921.20	133148.00	151865.70	292467.90	90332.12	358504.70	91532.38	946234.70	159840.00	90187.62	362332.90
gamma-L-Glutamyl-D-alanine	4396.54	2367519.00	1836448.00	1480091.00	3050.95	2920.70	7119.18	1256491.00	711729.80	26502.83	2662423.00	4360268.00	753570.30	2103098.00	1698269.00	211185.10	3388653.00
gamma-Glutamyl-gamma-aminobutyrate	28741.23	1918614.00	2037693.00	2702820.00	42113.09	56617.69	36346.25	1853495.00	1092245.00	40752.65	3238093.00	9696650.00	999939.70	3864689.00	1854262.00	285478.50	6186310.00
gamma-L-Glutamylputrescine	0.00	593278.60	1146094.00	2059344.00	0.00	0.00	0.00	1213328.00	1898603.00	0.00	2019062.00	1140474.00	199345.50	1375426.00	4091301.00	1403070.00	1942798.00
Phosphoserine	0.00	436809.40	2130934.00	42313.77	29019.73	33180.98	31883.68	1983997.00	244142.90	39337.02	56629.77	547219.90	88772.88	2094628.00	2365020.00	80337.14	2438720.00
Folate	7053300.00	0.00	0.00	0.00	7361336.00	7871450.00	6585764.00	0.00	0.00	7891324.00	0.00	0.00	9454.40	12996.94	0.00	0.00	0.00
10-Formyltetrahydrofolate	70788.21	0.00	0.00	0.00	150257.30	165600.60	35039.64	0.00	0.00	184240.20	0.00	0.00	0.00	0.00	0.00	0.00	0.00
Ornithine	1335172.00	967830.00	679497.10	291428.00	1370884.00	1289345.00	1283262.00	662503.10	191480.30	1363678.00	713950.60	1782553.00	439678.30	638509.60	438226.80	76761.70	1136705.00
L-Citrulline	3936.00	344670.30	161310.00	179251.30	4967.60	0.00	0.00	120844.10	154475.70	3807.29	80356.66	393486.50	28399.80	111512.20	137740.10	135095.90	149729.00
Cadaverine	111990.30	389846.20	33630.52	272060.40	24863.17	52545.84	14517.20	47687.16	191851.30	50012.36	78911.48	30829.14	198290.20	86002.51	39166.80	202361.10	33241.25
Putrescine	9466289.00	347000.50	106769.10	133546.70	10558500.00	10050260.00	9726371.00	76935.81	311676.70	10677250.00	155834.10	148123.90	128540.20	259697.50	84320.82	55328.31	158263.20
Spermidine	635121.40	2393428.00	16229180.00	10670910.00	453374.30	656473.70	823466.70	17838520.00	2883474.00	554365.80	20004800.00	3391191.00	8128904.00	21055950.00	7220362.00	7258806.00	22963950.00
Spermine	583490.10	333997.30	7629468.00	1744024.00	358698.20	493162.60	460896.80	7114992.00	1060489.00	501129.70	1255849.00	434785.00	6258974.00	4728770.00	1185734.00	1996594.00	2132541.00
N-Acetylneuraminate	8955.23	594721.10	438289.20	358246.20	7557.20	6196.37	6559.46	215656.40	203816.70	6298.73	509654.00	1560587.00	248135.80	573371.60	332370.20	96518.66	713104.40
alpha-D-Glucosamine 1-phosphate	22743.47	285283.90	196609.00	127589.90	21196.19	23022.48	39709.41	145322.30	118327.40	21764.17	345410.80	800324.70	103097.80	371380.20	234963.80	43332.62	268761.50
D-Glucosamine	0.00	70179.27	53881.26	36801.19	0.00	0.00	0.00	29251.27	87291.72	0.00	27137.42	155074.60	70598.23	46562.28	29111.79	10287.29	84152.04
Phosphocreatine	11589.10	64820.33	409565.60	1135895.00	18498.15	9146.41	11078.10	436398.20	388162.20	7701.40	103953.40	68291.65	83844.20	870691.20	628793.80	1729183.00	175330.70
Creatine	2207793.00	33022850.00	101865100.00	70588300.00	479076.30	719714.80	466712.00	89167420.00	37987360.00	791779.30	87919960.00	355945000.00	109287000.00	182850400.00	104452500.00	21765500.00	145565400.00
Creatinine	74141.43	144872.80	474652.40	382025.20	45514.25	39943.15	64667.77	424730.60	224006.80	50206.05	434218.80	1944918.00	643914.80	878620.10	417164.70	170813.10	752937.40
N-Acetyl-L-citrulline	2252906.00	351497.80	831270.50	842213.50	8451698.00	7589254.00	8525292.00	698110.20	716253.50	5498334.00	1237576.00	1792324.00	204589.10	828005.90	1321584.00	390330.40	1188791.00
N-Acetylornithine	8677.97	8142532.00	7435394.00	6958850.00	6031.16	5170.11	9994.90	5790586.00	5890930.00	7037.24	14004360.00	17540110.00	2395942.00	7588550.00	9222715.00	1787996.00	15912710.00
N-Succinyl-L-citrulline	0.00	661398.50	399883.00	328253.60	0.00	0.00	0.00	295811.10	125669.70	0.00	833519.60	3160395.00	190569.70	652121.00	424678.10	27247.01	1142465.00
Taurine	2503.80	741433.40	1085181.00	966218.70	3472.03	3051.19	0.00	554802.20	294948.60	0.00	680782.20	4801734.00	603679.60	1398188.00	284172.90	205004.50	1277387.00
5-Hydroxyindoleacetate	88522.01	1745900.00	1946639.00	1414826.00	160249.50	146192.70	246145.30	1250552.00	750650.90	94700.68	2208847.00	3186132.00	793971.50	1781315.00	1318426.00	196536.90	3319619.00
3-Methyleneoxindole	3756313.00	3382697.00	4864254.00	2414218.00	4405542.00	4777660.00	4564648.00	3916573.00	900180.70	4146678.00	3990701.00	4836530.00	4361584.00	3387013.00	1753330.00	488497.70	6417344.00
Indole	1662761.00	1534491.00	2092447.00	1187792.00	1859259.00	2005757.00	1860845.00	1805614.00	490603.10	2003052.00	1720617.00	2142962.00	1971886.00	1658132.00	896730.30	294010.20	2668192.00
Indole-3-acetate	53667580.00	161476.20	59550.45	29848.52	11811750.00	14581610.00	8980817.00	135275.70	61829.42	11260350.00	193619.10	405618.50	205272.50	324962.70	129694.40	16193.54	93471.62
6-Hydroxykynurenic acid	0.00	1656267.00	625632.10	136709.50	0.00	0.00	0.00	596661.40	99185.34	0.00	1680032.00	3422389.00	111932.10	1272093.00	1498670.00	70190.54	2628522.00
kynurenine	8108.67	84783.97	73967.91	106920.20	8203.78	7320.73	10095.83	39365.11	135937.40	7697.04	115776.30	442868.10	437550.60	308208.40	94480.95	42051.46	687209.20
2-Oxoadipate	4806824.00	4974.58	3667.65	2661.40	1018789.00	1225468.00	838140.80	2445.72	3091.08	1014488.00	3879.84	2921.51	3456.70	20123.74	5499.16	9512.61	14324.99
L-Adrenaline	3153065.00	364196.80	1131990.00	356229.00	6306594.00	6588060.00	4876932.00	1144416.00	351439.50	6116902.00	766955.20	825433.30	868838.80	960347.70	395590.30	478300.90	1089230.00
Serotonin	62692.74	49689.18	122306.80	300691.90	9882.87	15009.80	13943.20	114270.90	77246.54	16249.33	110161.90	46448.69	47051.67	95621.40	115555.80	41626.89	142840.00
Glycerol 3-phosphate	24997.99	1964816.00	1038411.00	90996.75	26457.48	11431.42	22677.09	682072.60	259928.80	17382.21	205481.60	506591.60	3703698.00	277888.80	252256.90	58160.34	565191.20
Sphingosine 1-phosphate	62697.99	56017.27	131008.60	52151.09	24184.53	68606.24	61001.22	123759.50	72233.31	17327.15	63605.02	35208.25	42814.35	80700.76	66990.63	57131.22	70134.30
Choline	232084.40	48711.57	50955.21	49003.55	218098.20	339418.90	206079.30	24920.66	17074.48	221575.80	63243.50	24767.74	14219.55	26406.54	18127.22	0.00	53128.49
L-Carnitine	19953530.00	8544780.00	17082070.00	4223678.00	20961510.00	21834630.00	20702640.00	12309220.00	5131254.00	21320500.00	14911020.00	38918590.00	8384562.00	20467970.00	5030280.00	5917148.00	19054520.00
acyl-C4-OH	32842.97	36723.76	42747.78	38951.83	60366.74	42753.87	28096.99	55452.25	19521.93	104047.40	41018.43	40055.12	34524.78	92377.88	55367.14	57418.23	29923.98
acyl-C4-DC	30423.37	40348.08	123088.90	97910.09	37026.75	45100.44	12330.96	165059.40	113420.80	89213.16	52766.72	640671.20	34177.49	232095.10	70453.30	114083.60	524971.40
acyl-C5:1	26939.76	169987.80	314540.60	133490.50	21336.92	13561.64	14740.37	311762.80	100110.00	12939.61	307499.60	524741.20	210269.30	274486.40	37903.77	63024.19	559881.00
acyl-C5-OH	10364.37	246596.60	674323.80	321786.20	11669.19	12790.82	11653.69	770447.00	1242403.00	8805.35	748790.80	1087251.00	402589.30	391839.70	581738.90	760958.50	799734.30
hexanoyl-L-carnitine	57384.64	142741.80	167589.00	449582.30	61821.64	82105.86	72731.80	131087.40	176111.90	33644.36	131375.40	187681.00	827723.70	141461.90	68033.02	74064.57	517399.60
L-octanoylcarnitine	23533.98	51032.59	60623.23	144715.50	39857.63	36885.83	19878.83	71221.21	42170.96	30419.82	49464.28	82616.77	357795.00	56435.71	50985.02	56070.52	164443.30
octenoyl-l-carnitine	0.00	40673.86	96189.49	47780.77	24033.74	41829.48	29028.92	38401.46	42580.93	17755.76	52700.04	47553.79	65827.38	29878.32	74070.71	68791.56	55797.16
O-Decanoyl-L-carnitine	19087.78	47019.66	28789.63	42420.81	19028.76	14146.83	23785.76	44145.78	42820.31	27511.96	38001.15	57382.59	52169.73	44294.76	41571.79	49940.27	38721.35
O-Decenoyl-L-carnitine	117679.40	131983.40	155747.40	135610.10	119418.80	201696.50	145155.50	117694.60	105092.10	93708.40	119059.20	107838.10	102615.90	143749.50	131015.60	115789.70	105514.20
O-dodecanoyl-carnitine	7487.72	9721.48	14517.33	8245.69	13712.53	14261.47	12578.31	10566.00	7292.09	9218.32	21095.85	10559.21	16140.25	14363.91	7304.19	22703.57	14657.76
O-dodecenoyl-carnitine	10970.44	14244.58	36241.05	7616.46	8556.70	13687.35	6472.21	14358.73	13243.91	11701.32	18232.20	14391.06	13448.58	8621.70	14920.39	14842.40	43141.71
O-tetradecanoyl-L-carnitine	18480.58	28250.36	3408.83	21053.15	27583.31	34168.07	22171.20	8767.21	22800.30	22572.42	6550.29	22204.08	16046.41	13860.66	18419.63	22524.35	4410.22
Tetradecenoyl Carnitine	64383.04	51424.30	18371.79	40945.50	43000.52	43062.95	39359.22	32872.08	45421.25	52179.38	25821.47	48186.66	50628.63	14023.14	42603.55	41032.23	16222.02
Hexadecenoyl-carnitine	38385.92	45941.29	17802.32	40702.75	85349.97	148238.50	110910.80	68094.21	32460.53	27913.23	277521.10	202785.90	361606.60	15210.21	555859.20	355633.40	107311.80
Octadecanoyl-L-carnitine	244364.00	71141.51	10191.32	4854.87	112707.50	28203.94	124268.40	99988.34	48791.27	134504.00	65365.05	34753.98	5400.08	34130.66	102741.60	254872.80	4703.32
O-octadecenoyl-L-carnitine	75237.55	3607.16	32390.50	74424.45	60949.66	411553.20	140152.30	281396.10	5904.04	6265.51	234719.60	137572.40	102192.60	2109.42	600992.00	773723.70	240172.20
Nicotinic acid	1583786.00	748609.20	4726582.00	1889686.00	1010815.00	1225733.00	1314638.00	4898676.00	1557211.00	1667172.00	5598034.00	3680075.00	1640589.00	7681350.00	4633298.00	1791390.00	4145757.00
Acetyl phosphate	7810650.00	7694378.00	7233058.00	7168992.00	9960435.00	7142506.00	6873264.00	6863730.00	6541642.00	7858262.00	6565922.00	8042516.00	8528216.00	6555574.00	6914708.00	8134314.00	6692634.00
N5-Methyl-L-glutamine	11888.89	1518371.00	2712216.00	3394497.00	35194.12	10395.49	9869.69	2178149.00	2238503.00	26906.48	3621985.00	3591581.00	586684.60	2939402.00	4749118.00	1135762.00	3814956.00
2-Methyleneglutarate	30104.56	140455.40	487666.90	257698.50	27062.33	51407.43	86547.03	312914.30	128385.80	61613.98	1515142.00	819954.60	259276.90	326485.70	525714.00	82843.93	525153.00
6-Lactoyl-5-6-7-8-tetrahydropterin	5862974.00	104440.50	80895.84	166075.10	5878706.00	5547680.00	6342334.00	65186.48	143120.90	5447020.00	195317.40	172277.70	0.00	50941.87	188990.40	28404.03	224227.10
3-Oxalomalate	14983900.00	16150280.00	14707120.00	14494720.00	18726200.00	16434360.00	14617110.00	13750340.00	14290460.00	14155400.00	15385480.00	15227570.00	16500230.00	13343200.00	15599200.00	16759000.00	13760260.00
cis-p-Coumarate	5995792.00	17613110.00	15903750.00	5170080.00	6851094.00	5219392.00	6331542.00	8211736.00	5598958.00	5991434.00	20053110.00	42711760.00	11177260.00	16955980.00	10334660.00	1425554.00	22162990.00
N6-Methyl-L-lysine	6884.09	255088.50	174612.80	133159.30	13487.66	4437.72	8289.47	161030.10	138784.30	6254.88	336860.20	1322283.00	134795.30	252378.20	195575.50	96867.84	436762.60
Riboflavin	378469.00	227963.50	66113.46	72603.35	981857.80	920387.10	759046.20	72858.00	54369.47	1106694.00	69079.66	126459.50	68101.98	83184.41	22779.08	21972.55	139142.90
Pyridoxamine	5709784.00	5120796.00	3872027.00	960749.20	6152166.00	5429734.00	6781788.00	3021808.00	1342193.00	5761262.00	4657386.00	6677974.00	2211949.00	3048861.00	2269532.00	478346.10	5728410.00
N-Amidino-L-aspartate	53975500.00	15953500.00	18437870.00	9635361.00	62562020.00	59504380.00	60831330.00	18915170.00	6553674.00	59359490.00	9625469.00	2420756.00	5928980.00	9517537.00	4774578.00	3992760.00	14630590.00
L-Noradrenaline	19679600.00	154801.30	57232.65	92445.98	23372930.00	23309310.00	22838730.00	219667.50	213325.80	23918180.00	67860.46	32345.47	158762.70	162129.80	73257.52	97372.52	170300.60
2-Oxo-7-methylthioheptanoic acid	12391050.00	11625220.00	9451415.00	2342838.00	10047120.00	12155200.00	11205780.00	6329510.00	2689318.00	12806450.00	10787200.00	13714110.00	5416644.00	8168556.00	5719380.00	973075.00	13877320.00
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	KEGG or HMDB ID	mz	r.t.
L-alanine	C00041	90.0554	0.67
L-arginine	C00062	175.1185	0.65
L-asparagine	C00152	133.0603	0.68
L-aspartate	C00049	134.0446	0.72
L-cysteine	C00097	122.0271	0.54
L-glutamate	C00025	148.0602	0.67
L-glutamine	C00064	147.0761	0.67
glycine	C00037	76.0400	1.73
L-histidine	C00135	156.0765	0.61
L-leucine	C00123	132.1017	0.68
L-lysine	C00047	147.1125	0.60
L-methionine	C00073	150.0581	0.68
L-phenylalanine	C00079	166.0858	1.25
L-proline	C00148	116.0707	0.67
L-serine	C00065	106.0501	0.69
L-threonine	C00188	120.0656	0.67
L-tryptophan	C00078	205.0967	1.71
L-tyrosine	C00082	182.0801	0.69
L-valine	C00183	118.0863	0.68
L-cystine	C00491	241.0296	0.70
Adenosine	C00212	268.1032	1.72
CMP	C00055	324.0577	0.78
Hypoxanthine	C00262	137.0456	0.73
3',5'-Cyclic AMP	C00575	330.0615	0.69
4-Pyridoxate	C00847	184.0578	0.67
Nicotinamide	C00153	123.0552	0.75
NAD+	C00003	665.1177	0.75
D-Glucono-1-5-lactone 6-phosphate	C01236	259.0204	4.58
Cys-Gly	C01419	179.0480	0.70
gamma-L-Glutamyl-L-cysteine	C00669	251.0687	0.77
gamma-Glutamyl-Se-methylselenocysteine	C05695	313.0309	0.72
gamma-L-Glutamyl-D-alanine	C03738	219.0979	0.75
gamma-Glutamyl-gamma-aminobutyrate	C15767	233.1137	1.09
gamma-L-Glutamylputrescine	C15699	218.1493	0.60
Phosphoserine	C02532	186.0172	0.65
Folate	C00504	442.1461	1.70
10-Formyltetrahydrofolate	C00234	474.1820	1.89
Ornithine	C01602	133.0978	0.66
L-Citrulline	C00327	176.1042	0.65
Cadaverine	C01672	103.1232	0.65
Putrescine	C00134	89.1078	0.60
Spermidine	C00315	146.1649	0.60
Spermine	C00750	203.2226	0.60
N-Acetylneuraminate	C00270	310.1118	0.87
alpha-D-Glucosamine 1-phosphate	C06156	260.0512	0.67
D-Glucosamine	C00329	180.0876	1.15
Phosphocreatine	C02305	212.0419	0.75
Creatine	C00300	132.0766	0.64
Creatinine	C00791	114.0664	0.86
N-Acetyl-L-citrulline	C15532	218.1130	0.70
N-Acetylornithine	C00437	175.1086	0.63
N-Succinyl-L-citrulline	C18048	276.1181	0.67
Taurine	C00245	126.0217	0.69
5-Hydroxyindoleacetate	C05635	192.0654	1.42
3-Methyleneoxindole	C02796	146.0598	1.71
Indole	C00463	118.0652	1.71
Indole-3-acetate	C00954	176.0715	1.78
6-Hydroxykynurenic acid	C08480	206.0475	0.79
kynurenine	C00328	209.0924	0.93
2-Oxoadipate	C00322	161.0447	1.75
L-Adrenaline	C00788	184.0962	0.70
Serotonin	C00780	177.1020	1.74
Glycerol 3-phosphate	C00093	173.0219	0.76
Sphingosine 1-phosphate	C06124	380.2587	1.78
Choline	C00114	105.1134	0.66
L-Carnitine	C00318	162.1121	0.66
acyl-C4-OH	HMDB13127	248.1497	3.78
acyl-C4-DC	HMDB13133	262.1300	1.75
acyl-C5:1	HMDB02366	244.1537	1.75
acyl-C5-OH	ac107	262.1641	1.03
hexanoyl-L-carnitine	HMDB00756	260.1848	1.80
L-octanoylcarnitine	HMDB00791	288.2159	1.85
octenoyl-l-carnitine	ac111	286.2002	1.84
O-Decanoyl-L-carnitine	HMDB00651	316.2472	1.93
O-Decenoyl-L-carnitine	CID57357170	314.2372	2.32
O-dodecanoyl-carnitine	HMDB02250	344.2784	1.96
O-dodecenoyl-carnitine	HMDB13326	342.2628	1.89
O-tetradecanoyl-L-carnitine	HMDB05066	372.3090	2.34
Tetradecenoyl Carnitine	HMDB13329	370.2934	2.39
Hexadecenoyl-carnitine	HMDB06317	398.3253	2.06
Octadecanoyl-L-carnitine	HMDB00848	428.3719	2.55
O-octadecenoyl-L-carnitine	HMDB06351	426.3560	2.65
Nicotinic acid	C00253	124.0396	0.58
Acetyl phosphate	C00227	140.9952	3.79
N5-Methyl-L-glutamine	C03153	161.0926	0.83
2-Methyleneglutarate	C02930	145.0493	0.73
6-Lactoyl-5-6-7-8-tetrahydropterin	C04244	240.1066	0.69
3-Oxalomalate	C01990	207.0168	3.79
cis-p-Coumarate	C06738	165.0542	0.69
N6-Methyl-L-lysine	C02728	161.1285	0.58
Riboflavin	C00255	377.1443	1.72
Pyridoxamine	C00534	169.0947	0.61
N-Amidino-L-aspartate	C03139	176.0655	0.69
L-Noradrenaline	C00547	170.0807	0.69
2-Oxo-7-methylthioheptanoic acid	C17220	191.0761	0.61
METABOLITES_END
#END