#METABOLOMICS WORKBENCH NicholasDevanney_20230120_133842 DATATRACK_ID:3695 STUDY_ID:ST002451 ANALYSIS_ID:AN003999 PROJECT_ID:PR001580
VERSION             	1
CREATED_ON             	January 20, 2023, 4:22 pm
#PROJECT
PR:PROJECT_TITLE                 	APOE modulates microglial immunometabolism in response to age, amyloid
PR:PROJECT_TITLE                 	pathology, and inflammatory challenge
PR:PROJECT_SUMMARY               	The E4 allele of Apolipoprotein E (APOE) is associated with both metabolic
PR:PROJECT_SUMMARY               	dysfunction and a heightened pro-inflammatory response – two findings that may
PR:PROJECT_SUMMARY               	be intrinsically linked through the concept of immunometabolism. Here, we
PR:PROJECT_SUMMARY               	combined bulk, single-cell, and spatial transcriptomics with cell-specific and
PR:PROJECT_SUMMARY               	spatially resolved metabolic analyses to systematically address the role of APOE
PR:PROJECT_SUMMARY               	across age, neuroinflammation, and AD pathology. RNAseq highlighted
PR:PROJECT_SUMMARY               	immunometabolic changes across the APOE4 glial transcriptome, specifically in
PR:PROJECT_SUMMARY               	subsets of metabolically distinct microglia enriched in the E4 brain during
PR:PROJECT_SUMMARY               	aging or following an inflammatory challenge. E4 microglia display increased
PR:PROJECT_SUMMARY               	Hif1α expression, a disrupted TCA cycle, and are inherently pro-glycolytic,
PR:PROJECT_SUMMARY               	while spatial transcriptomics and MALDI mass spectrometry imaging highlight an
PR:PROJECT_SUMMARY               	E4-specific response to amyloid that is characterized by widespread alterations
PR:PROJECT_SUMMARY               	in lipid metabolism. Taken together, our findings emphasize a central role for
PR:PROJECT_SUMMARY               	APOE in regulating microglial immunometabolism.
PR:INSTITUTE                     	University of Kentucky
PR:DEPARTMENT                    	Physiology
PR:LABORATORY                    	Lance Johnson; Josh Morganti
PR:LAST_NAME                     	Devanney
PR:FIRST_NAME                    	Nicholas
PR:ADDRESS                       	Physiology, 760 Press Ave, Healthy Kentucky Research Bldg, Rm152, Lexington,
PR:ADDRESS                       	Kentucky, 40508, USA
PR:EMAIL                         	Nicholas.Devanney@uky.edu
PR:PHONE                         	8593238083
PR:PROJECT_COMMENTS              	Part 2 of 3
#STUDY
ST:STUDY_TITLE                   	APOE modulates microglial immunometabolism in response to age, amyloid
ST:STUDY_TITLE                   	pathology, and inflammatory challenge (Part 2 of 3)
ST:STUDY_SUMMARY                 	The E4 allele of Apolipoprotein E (APOE) is associated with both metabolic
ST:STUDY_SUMMARY                 	dysfunction and a heightened pro-inflammatory response – two findings that may
ST:STUDY_SUMMARY                 	be intrinsically linked through the concept of immunometabolism. Here, we
ST:STUDY_SUMMARY                 	combined bulk, single-cell, and spatial transcriptomics with cell-specific and
ST:STUDY_SUMMARY                 	spatially resolved metabolic analyses to systematically address the role of APOE
ST:STUDY_SUMMARY                 	across age, neuroinflammation, and AD pathology. RNAseq highlighted
ST:STUDY_SUMMARY                 	immunometabolic changes across the APOE4 glial transcriptome, specifically in
ST:STUDY_SUMMARY                 	subsets of metabolically distinct microglia enriched in the E4 brain during
ST:STUDY_SUMMARY                 	aging or following an inflammatory challenge. E4 microglia display increased
ST:STUDY_SUMMARY                 	Hif1α expression, a disrupted TCA cycle, and are inherently pro-glycolytic,
ST:STUDY_SUMMARY                 	while spatial transcriptomics and MALDI mass spectrometry imaging highlight an
ST:STUDY_SUMMARY                 	E4-specific response to amyloid that is characterized by widespread alterations
ST:STUDY_SUMMARY                 	in lipid metabolism. Taken together, our findings emphasize a central role for
ST:STUDY_SUMMARY                 	APOE in regulating microglial immunometabolism.
ST:INSTITUTE                     	University of Kentucky
ST:DEPARTMENT                    	Physiology
ST:LABORATORY                    	Lance Johnson; Josh Morganti
ST:LAST_NAME                     	Devanney
ST:FIRST_NAME                    	Nicholas
ST:ADDRESS                       	Physiology, 760 Press Ave, Healthy Kentucky Research Bldg, Rm152, Lexington,
ST:ADDRESS                       	Kentucky, 40508, USA
ST:EMAIL                         	Nicholas.Devanney@uky.edu
ST:PHONE                         	8593238083
ST:STUDY_COMMENTS                	Part 2 of 3
#SUBJECT
SU:SUBJECT_TYPE                  	Mammal
SU:SUBJECT_SPECIES               	Mus musculus
SU:TAXONOMY_ID                   	10090
SU:GENOTYPE_STRAIN               	APOE-targeted replacement mice homozygous for human E3
SU:GENOTYPE_STRAIN               	(B6.129P2-Apoe^tm2(APOE*3)Mae N8, Taconic #1548-F) or human E4 (B6.129P2-
SU:GENOTYPE_STRAIN               	Apoe^tm3(APOE*4)Mae N8, Taconic #1549-F) alleles
SU:AGE_OR_AGE_RANGE              	P0-P3
SU:GENDER                        	Pooled
#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           	-	47_3_1	Group:E3_control | APOE genotype:E3/E3 | Treatment:Control	RAW_FILE_NAME=47_3_1.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_3_2	Group:E3_control | APOE genotype:E3/E3 | Treatment:Control	RAW_FILE_NAME=47_3_2.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_3_3	Group:E3_control | APOE genotype:E3/E3 | Treatment:Control	RAW_FILE_NAME=47_3_3.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_3_4	Group:E3_control | APOE genotype:E3/E3 | Treatment:Control	RAW_FILE_NAME=47_3_4.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_3_9	Group:E3_control | APOE genotype:E3/E3 | Treatment:Control	RAW_FILE_NAME=47_3_9.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_3_10	Group:E3_control | APOE genotype:E3/E3 | Treatment:Control	RAW_FILE_NAME=47_3_10.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_3_11	Group:E3_control | APOE genotype:E3/E3 | Treatment:Control	RAW_FILE_NAME=47_3_11.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_3_12	Group:E3_control | APOE genotype:E3/E3 | Treatment:Control	RAW_FILE_NAME=47_3_12.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_3_5	Group:E3_proinflammatory | APOE genotype:E3/E3 | Treatment:Proinflammatory	RAW_FILE_NAME=47_3_5.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_3_6	Group:E3_proinflammatory | APOE genotype:E3/E3 | Treatment:Proinflammatory	RAW_FILE_NAME=47_3_6.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_3_7	Group:E3_proinflammatory | APOE genotype:E3/E3 | Treatment:Proinflammatory	RAW_FILE_NAME=47_3_7.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_3_8	Group:E3_proinflammatory | APOE genotype:E3/E3 | Treatment:Proinflammatory	RAW_FILE_NAME=47_3_8.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_3_13	Group:E3_proinflammatory | APOE genotype:E3/E3 | Treatment:Proinflammatory	RAW_FILE_NAME=47_3_13.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_3_14	Group:E3_proinflammatory | APOE genotype:E3/E3 | Treatment:Proinflammatory	RAW_FILE_NAME=47_3_14.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_3_15	Group:E3_proinflammatory | APOE genotype:E3/E3 | Treatment:Proinflammatory	RAW_FILE_NAME=47_3_15.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_3_16	Group:E3_proinflammatory | APOE genotype:E3/E3 | Treatment:Proinflammatory	RAW_FILE_NAME=47_3_16.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_4_1	Group:E4_control | APOE genotype:E4/E4 | Treatment:Control	RAW_FILE_NAME=47_4_1.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_4_2	Group:E4_control | APOE genotype:E4/E4 | Treatment:Control	RAW_FILE_NAME=47_4_2.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_4_3	Group:E4_control | APOE genotype:E4/E4 | Treatment:Control	RAW_FILE_NAME=47_4_3.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_4_4	Group:E4_control | APOE genotype:E4/E4 | Treatment:Control	RAW_FILE_NAME=47_4_4.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_4_9	Group:E4_control | APOE genotype:E4/E4 | Treatment:Control	RAW_FILE_NAME=47_4_9.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_4_10	Group:E4_control | APOE genotype:E4/E4 | Treatment:Control	RAW_FILE_NAME=47_4_10.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_4_12	Group:E4_control | APOE genotype:E4/E4 | Treatment:Control	RAW_FILE_NAME=47_4_12.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_4_6	Group:E4_proinflammatory | APOE genotype:E4/E4 | Treatment:Proinflammatory	RAW_FILE_NAME=47_4_6.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_4_7	Group:E4_proinflammatory | APOE genotype:E4/E4 | Treatment:Proinflammatory	RAW_FILE_NAME=47_4_7.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_4_8	Group:E4_proinflammatory | APOE genotype:E4/E4 | Treatment:Proinflammatory	RAW_FILE_NAME=47_4_8.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_4_13	Group:E4_proinflammatory | APOE genotype:E4/E4 | Treatment:Proinflammatory	RAW_FILE_NAME=47_4_13.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_4_14	Group:E4_proinflammatory | APOE genotype:E4/E4 | Treatment:Proinflammatory	RAW_FILE_NAME=47_4_14.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_4_15	Group:E4_proinflammatory | APOE genotype:E4/E4 | Treatment:Proinflammatory	RAW_FILE_NAME=47_4_15.CDF
SUBJECT_SAMPLE_FACTORS           	-	47_4_16	Group:E4_proinflammatory | APOE genotype:E4/E4 | Treatment:Proinflammatory	RAW_FILE_NAME=47_4_16.CDF
#COLLECTION
CO:COLLECTION_SUMMARY            	Primary microglia were plated at 7x10^6 cells/well in 6-well plates (VWR
CO:COLLECTION_SUMMARY            	#10062-894) and incubated at 5% CO2 37°C. Upon reaching confluence, cells were
CO:COLLECTION_SUMMARY            	washed with warm, sterile phosphate-buffered saline (PBS; Thomas
CO:COLLECTION_SUMMARY            	#QZY-11666789001-4L) to remove traces of non-13C media and then incubated in
CO:COLLECTION_SUMMARY            	glucose- and sodium pyruvate-free DMEM (Thermo #11966-025) containing 2mM
CO:COLLECTION_SUMMARY            	GlutaMAX (Thermo #35050-061), 1% penicillin/streptomycin, and 10mM universally
CO:COLLECTION_SUMMARY            	labelled 13C-glucose (Cambridge Isotope Laboratories # CLM-1396-PK) for two
CO:COLLECTION_SUMMARY            	hours with either a pro-inflammatory cocktail of 20ng/ml interferon-γ (IFNγ,
CO:COLLECTION_SUMMARY            	R&D Systems #485-MI-100) and 50ng/ml tumor necrosis factor α (TNFα, R&D
CO:COLLECTION_SUMMARY            	Systems #410-MT-025) or vehicle control. Cells were then removed from the
CO:COLLECTION_SUMMARY            	incubator and washed with warm 0.9% NaCl solution. Culture plates were placed on
CO:COLLECTION_SUMMARY            	a bed of crushed dry ice and 1mL of ice cold 50% methanol (HPLC-grade, Sigma
CO:COLLECTION_SUMMARY            	#A456-4) was added to quench cellular metabolic activity followed by a 10 minute
CO:COLLECTION_SUMMARY            	incubation at -80°C to ensure cell lysis. After removing from the freezer,
CO:COLLECTION_SUMMARY            	cells were detached with a cell scraper (VWR #10062-906) and the entire contents
CO:COLLECTION_SUMMARY            	collected into a microcentrifuge tube, vortexed briefly, and placed on ice until
CO:COLLECTION_SUMMARY            	all samples were collected. The tubes were then placed on a Disruptor Genie Cell
CO:COLLECTION_SUMMARY            	Disruptor Homogenizer (Scientific Industries) for 5 min at 3,000 rpm. Tubes were
CO:COLLECTION_SUMMARY            	then centrifuged at 20,000 x g for 10 min at 4 °C. The supernatant containing
CO:COLLECTION_SUMMARY            	polar metabolites was isolated to a new tube and stored at -80C until use.
CO:SAMPLE_TYPE                   	Brain
#TREATMENT
TR:TREATMENT_SUMMARY             	APOE3/3 and APOE4/4 primary microglia were treated for 2 hours with a
TR:TREATMENT_SUMMARY             	pro-inflammatory cocktail of 20ng/ml interferon-γ (IFNγ, R&D Systems
TR:TREATMENT_SUMMARY             	#485-MI-100) and 50ng/ml tumor necrosis factor α (TNFα, R&D Systems
TR:TREATMENT_SUMMARY             	#410-MT-025) or vehicle control.
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	The supernatant fraction containing polar metabolites was thawed gently on ice
SP:SAMPLEPREP_SUMMARY            	and dried at 10-3 mbar using a CentriVap vacuum concentrator (LabConco) to
SP:SAMPLEPREP_SUMMARY            	evaporate methanol. The dried polar metabolite pellet was derivatized by a
SP:SAMPLEPREP_SUMMARY            	two-step methoxyamine protocol first by addition of 70µL methoxyamine HCl
SP:SAMPLEPREP_SUMMARY            	(Sigma-Aldrich #226904-5G) in pyridine (20 mg/mL; Sigma-Aldrich #TS25730) to
SP:SAMPLEPREP_SUMMARY            	each pellet followed by 90 min dry heat incubation at 30°C. Samples were then
SP:SAMPLEPREP_SUMMARY            	centrifuged at 20,000 x g for 10 minutes after which 50µL of each sample was
SP:SAMPLEPREP_SUMMARY            	transferred to an amber V-shaped glass chromatography vial (Agilent #5184-3554)
SP:SAMPLEPREP_SUMMARY            	containing 80µL N-methyl-trimethylsilyl-trifluoroacetamide (MSTFA; ThermoFisher
SP:SAMPLEPREP_SUMMARY            	#TS48915) and gently vortexed followed by 30 min dry heat incubation at 37°C.
SP:EXTRACTION_METHOD             	50% ice-cold methanol
SP:EXTRACT_STORAGE               	-80℃
SP:SAMPLE_DERIVATIZATION         	MSTFA
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_TYPE           	GC
CH:INSTRUMENT_NAME               	Agilent 8890
CH:COLUMN_NAME                   	Agilent HP5-MS (30m x 0.25mm, 0.25 um)
CH:SOLVENT_A                     	N/A
CH:SOLVENT_B                     	N/A
CH:FLOW_GRADIENT                 	N/A
CH:FLOW_RATE                     	0.581 mL/min
CH:COLUMN_TEMPERATURE            	60°C, rising at 10°C/min to 325°C, and held for 10 min
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:INSTRUMENT_NAME               	Agilent 5977B
MS:INSTRUMENT_TYPE               	Single quadrupole
MS:MS_TYPE                       	EI
MS:ION_MODE                      	POSITIVE
MS:MS_COMMENTS                   	Metabolites were identified and quantified using DExSI v1.11
MS:MS_COMMENTS                   	(https://github.com/DExSI/DExSI)
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	Fractional Enrichment (adjusted for natural abundance)
MS_METABOLITE_DATA_START
Samples	47_3_1	47_3_10	47_3_11	47_3_12	47_3_13	47_3_14	47_3_15	47_3_16	47_3_2	47_3_3	47_3_4	47_3_5	47_3_6	47_3_7	47_3_8	47_3_9	47_4_1	47_4_10	47_4_12	47_4_13	47_4_14	47_4_15	47_4_16	47_4_2	47_4_3	47_4_4	47_4_6	47_4_7	47_4_8	47_4_9
Factors	Group:E3_control | APOE genotype:E3/E3 | Treatment:Control	Group:E3_control | APOE genotype:E3/E3 | Treatment:Control	Group:E3_control | APOE genotype:E3/E3 | Treatment:Control	Group:E3_control | APOE genotype:E3/E3 | Treatment:Control	Group:E3_proinflammatory | APOE genotype:E3/E3 | Treatment:Proinflammatory	Group:E3_proinflammatory | APOE genotype:E3/E3 | Treatment:Proinflammatory	Group:E3_proinflammatory | APOE genotype:E3/E3 | Treatment:Proinflammatory	Group:E3_proinflammatory | APOE genotype:E3/E3 | Treatment:Proinflammatory	Group:E3_control | APOE genotype:E3/E3 | Treatment:Control	Group:E3_control | APOE genotype:E3/E3 | Treatment:Control	Group:E3_control | APOE genotype:E3/E3 | Treatment:Control	Group:E3_proinflammatory | APOE genotype:E3/E3 | Treatment:Proinflammatory	Group:E3_proinflammatory | APOE genotype:E3/E3 | Treatment:Proinflammatory	Group:E3_proinflammatory | APOE genotype:E3/E3 | Treatment:Proinflammatory	Group:E3_proinflammatory | APOE genotype:E3/E3 | Treatment:Proinflammatory	Group:E3_control | APOE genotype:E3/E3 | Treatment:Control	Group:E4_control | APOE genotype:E4/E4 | Treatment:Control	Group:E4_control | APOE genotype:E4/E4 | Treatment:Control	Group:E4_control | APOE genotype:E4/E4 | Treatment:Control	Group:E4_proinflammatory | APOE genotype:E4/E4 | Treatment:Proinflammatory	Group:E4_proinflammatory | APOE genotype:E4/E4 | Treatment:Proinflammatory	Group:E4_proinflammatory | APOE genotype:E4/E4 | Treatment:Proinflammatory	Group:E4_proinflammatory | APOE genotype:E4/E4 | Treatment:Proinflammatory	Group:E4_control | APOE genotype:E4/E4 | Treatment:Control	Group:E4_control | APOE genotype:E4/E4 | Treatment:Control	Group:E4_control | APOE genotype:E4/E4 | Treatment:Control	Group:E4_proinflammatory | APOE genotype:E4/E4 | Treatment:Proinflammatory	Group:E4_proinflammatory | APOE genotype:E4/E4 | Treatment:Proinflammatory	Group:E4_proinflammatory | APOE genotype:E4/E4 | Treatment:Proinflammatory	Group:E4_control | APOE genotype:E4/E4 | Treatment:Control
Pyruvic acid	73.7033551	27.86065381	37.13190722	46.60241407	49.60560957	27.51108433	79.12872878	52.61921617	43.70983361	44.56509299	85.15340672	62.48673442	39.58435399	52.65937904	44.44812968	67.31029927	54.82112392	35.79953096	30.73494682	50.11426557	33.56302892	55.66063718	36.54578033	60.86801665	61.33121599	61.3855051	65.11339702	28.72169818	59.89044304	36.8315281
Pyruvic acid_13C_1	-3.358709209	-2.802629989	-3.735056162	-4.687458911	-4.989773155	-2.767328851	-2.957435275	-1.310175914	-4.397100684	-4.482832618	-3.688409145	-2.25206784	-3.982049423	-2.570921485	-1.887401392	-4.475415015	-5.514656465	-3.601132515	-3.091784008	-5.041396782	-1.071776551	-5.59916197	-0.609209819	-6.122857151	-3.585328885	-1.373230413	0.391565915	-2.889052794	-4.064479709	-3.704935679
Pyruvic acid_13C_2	-1.160930359	-0.920432651	1.317814312	-1.53969548	-1.638871286	-0.908925935	-3.117854401	-0.60379387	-1.444375972	-1.472460658	-3.304188122	0.107118299	-1.308079719	-2.014175819	-0.903553912	-0.865213395	-1.811508039	-1.183017325	-1.015679102	-1.655871291	-1.340793078	2.469336166	-1.516215732	-2.011271449	-0.404117526	-0.208114677	-2.849762035	-0.949033035	-2.176123653	-1.216883918
Pyruvic acid_13C_3	30.81628447	75.86240883	65.28533463	59.62474032	57.02303487	76.16517046	26.94656089	49.29475362	62.13164304	61.39020029	21.83919054	39.65821512	65.70577515	51.92571826	58.34282562	38.03032914	52.50504058	68.98461888	73.37251629	56.58300251	68.84954071	47.46918863	65.57964522	47.26611195	42.65823042	40.19583999	37.3447991	75.11638765	46.35016032	68.09029149
Lactic acid	87.26464779	73.95039846	71.30749528	90.2547858	82.49027196	46.93854414	50.48690722	77.34200502	79.35094021	49.60481566	62.85763244	65.57993946	48.01605425	31.78803455	75.19876801	61.75693055	58.81813922	66.34121843	76.66644061	50.2011948	42.42137828	0	46.1971792	51.76042928	69.46822876	31.92762084	45.07075014	36.86427538	51.69579421	33.15856952
Lactic acid_13C_1	2.991679698	2.589703002	1.858712424	1.808041831	2.47163255	-3.247081089	2.646005121	1.216157751	0.291267923	3.677230311	1.348353663	2.097852314	-0.006227943	-0.689814092	1.84462771	4.446564495	1.288096847	1.097642002	1.277536423	-2.40014844	2.701893918	0	0.830031311	-8.805564236	1.766116547	2.859035883	0.634307895	5.160658398	1.446005475	1.257349268
Lactic acid_13C_2	1.543802079	1.080209758	2.409470698	0.468622322	2.062567865	3.867444237	-1.69806231	0.35244832	0.728970275	2.639298949	2.278899325	2.797463733	0.571240745	3.766102476	-0.020486254	1.858255784	5.00585294	3.410805654	1.242313606	4.496746199	1.993703097	0	2.599822661	-2.883676419	0.713319972	5.810959938	7.293100395	3.277510556	-0.315646309	4.537943707
Lactic acid_13C_3	8.199870434	22.37968878	24.4243216	7.468550043	12.97552762	52.44109271	48.56514997	21.08938891	19.62882159	44.07865508	33.51511457	29.52474449	51.41893295	65.13567707	22.97709053	31.93824917	34.88791099	29.15033392	20.81370936	47.70220744	52.88302471	0	50.37296683	59.92881137	28.05233472	59.40238334	47.00184157	54.69755566	47.17384662	61.04613751
beta-Alanine	104.8478489	98.0143368	86.96643088	104.6203335	0	104.4669112	0	96.89985937	102.9537124	104.7219461	102.2481643	90.10250061	96.40837093	101.7423714	105.9048007	104.6685171	100.3531361	99.4356538	104.1810278	96.84067924	101.091937	0	101.2166826	102.7118343	102.3140065	103.7284279	102.5008095	98.66935636	0	102.8291472
beta-Alanine_13C_1	-3.291342254	2.645256602	11.92578935	-3.123459221	0	-2.764495878	0	3.490846708	-3.286877098	-4.029668635	-1.161525885	8.924562261	6.289985945	-0.082303331	-4.170376828	-4.18878763	0.197894841	-0.222947515	-2.809140346	2.566411342	-0.648558943	0	-2.74199868	-0.985299901	-2.381826486	-3.864674259	-4.088762586	2.782763172	0	-2.305318589
beta-Alanine_13C_2	-2.523670298	-1.684321856	-1.037140276	-0.938757335	0	-2.350989893	0	-1.170867848	-1.874344558	-1.308658839	-1.549654694	-3.193886548	-1.538227688	-2.710704107	-2.608475466	-1.386419271	-0.647353247	-1.384384297	-1.521568077	-0.225821568	-0.406024174	0	0.23739432	-1.956110506	-0.074977924	-1.054591057	1.038776957	-2.389261815	0	-1.139393169
beta-Alanine_13C_3	0.967163629	1.024728457	2.144920046	-0.558116923	0	0.648574527	0	0.780161767	2.207509291	0.616381408	0.463016275	4.166823673	-1.160129182	1.050636024	0.874051616	0.90668985	0.09632232	2.171678011	0.14968063	0.818730989	-0.03735385	0	1.287921804	0.229576073	0.142797944	1.190837387	0.549176139	0.937142286	0	0.615564519
Leucine	101.7699823	104.1697619	104.0853458	104.0455805	105.0242299	104.1997523	105.5425041	103.6190315	103.3457533	101.498168	103.3391695	102.7543606	104.0091128	103.2549544	103.7685138	103.462805	103.4639132	103.8604531	103.4366289	103.7003741	103.5527211	0	103.9231387	103.9836018	104.3564673	103.7724516	102.6248022	103.9861619	0	103.2064071
Leucine_13C_1	-1.737444355	-2.004293589	-1.928850653	-2.12735763	-2.605532863	-2.015750053	-3.045302794	-1.68389297	-2.969848107	-1.638638216	-2.381215094	-1.659418132	-1.9809969	-2.026673372	-1.893862753	-1.674711198	-1.714164886	-2.046572335	-1.823316946	-1.849477664	-1.682864117	0	-1.962636442	-2.511271889	-1.785848883	-1.818513479	-2.60753976	-2.066899697	0	-1.081104431
Leucine_13C_2	-3.532517248	-3.627716409	-3.863968229	-3.741542574	-3.983555622	-3.664361072	-3.964739052	-3.600595498	-3.734150126	-3.518606988	-3.471521899	-3.977626787	-3.999050714	-3.600807372	-3.553880616	-3.522835593	-3.618766059	-3.619123154	-3.820096143	-3.844146398	-3.786165633	0	-3.706520023	-3.754059465	-3.465911431	-3.708315403	-3.88699993	-3.922544477	0	-3.644559695
Leucine_13C_3	1.470418949	0.603161426	0.738149859	1.196174918	0.495256241	0.682466686	0.896063639	0.675633957	1.953791722	1.92867312	1.121959483	2.186276972	1.148383291	1.763340855	0.887072924	0.838575142	1.165166926	0.922135088	1.012197802	1.239079697	1.179132141	0	0.781264283	0.943771017	0.204925041	1.047082469	2.098490535	1.234887002	0	1.036486823
Leucine_13C_4	0.106642935	0.077332203	0.074544175	0.028694084	0.102226804	0.116414661	0.066041238	0.069254657	-0.038289204	0.112431854	0.209865234	0.0505112	0.043106051	-0.028086771	0.092881316	0.051458904	0.025957753	0.048371847	0.048013688	0.028534661	0.031349904	0	0.064416493	0.052616428	0.106309772	0.040317249	-0.045677688	0.032392365	0	0.037538576
Leucine_13C_5	0.85624172	0.803094478	0.85551557	0.434458534	1.067862285	0.694285062	0.559357507	0.951346831	0.708342128	0.839208304	0.874287138	0.558338452	0.605199423	0.619207855	0.563446801	0.931550772	0.570985454	0.841115421	1.078519452	0.800369272	0.778628759	0	0.86347979	1.223491225	0.646329565	0.629389039	1.998051344	0.725088708	0	0.492263694
Leucine_13C_6	1.066675655	-0.021339998	0.039263446	0.163992141	-0.100486774	-0.012807602	-0.053924618	-0.030778466	0.734400285	0.778763908	0.307455641	0.087557705	0.174246088	0.018064372	0.135828576	-0.086843071	0.106907643	-0.006379946	0.068053264	-0.074733637	-0.072802151	0	0.036857189	0.061850849	-0.062271389	0.037588562	-0.181126742	0.010914184	0	-0.047032034
Isoleucine	101.9907682	102.5844664	102.8402718	103.3208254	99.53960634	102.9327788	101.612481	100.290906	102.8456484	102.3779486	102.7295771	102.1068577	103.7581996	101.9119262	102.5484065	102.0336112	103.3656901	102.6395036	100.4790521	102.4203981	103.0597524	0	102.3626626	101.316002	103.1057644	102.4048616	99.23355042	101.096932	0	102.4630617
Isoleucine_13C_1	-0.945601903	-1.254275389	-0.991334502	-1.211224084	-0.788622366	-1.113200589	-1.69647858	-0.368028517	-1.1894752	-1.080714222	-0.723515562	-0.701095796	-1.204831898	-0.062449288	-0.806065986	-0.632330072	-1.357781684	-1.102931906	-0.644484421	-0.013733266	-0.992279751	0	-0.422146701	-0.629209164	-1.157655631	-0.694441146	-0.171321216	-0.490342734	0	-1.157168333
Isoleucine_13C_2	-3.504635669	-3.426734369	-3.382187302	-3.847859836	-3.725020581	-3.336885353	-3.740290196	-3.3527681	-3.517516608	-3.434728131	-3.586685324	-3.251603527	-3.412985947	-3.528403381	-3.312977686	-3.461895812	-3.440825767	-3.383485905	-3.525660893	-3.961507079	-3.308217055	0	-3.478180557	-3.464280328	-3.385167633	-3.295943207	-3.970280981	-3.450348454	0	-3.361968345
Isoleucine_13C_3	0.757464562	0.996386991	0.422652082	0.715769555	3.943705448	0.571007393	3.114402777	1.866979632	1.029318457	0.9793726	0.486663358	0.625537234	0.432851536	0.657219185	0.633057422	0.815818643	0.460039589	0.987820228	2.386367563	0.511542716	0.697357079	0	0.81909755	1.647414037	0.456856338	0.657044854	3.548914077	1.671348758	0	0.881309347
Isoleucine_13C_4	0.110727488	0.032805539	0.091251832	0.07481929	-0.221059342	0.067225466	-0.144503966	-0.008450834	0.033331255	0.090297876	0.08422213	0.134800545	0.08274634	0.065514664	0.060210302	0.049513813	0.081745666	0.084251156	-0.007610968	0.095875683	0.054463	0	0.049456345	0.025472123	0.079493436	0.057199329	-0.176626099	0.024148707	0	0.040428785
Isoleucine_13C_5	0.960076439	0.976936352	1.070202075	1.045460657	1.372297896	0.913367305	0.573267303	1.573906738	0.761073733	0.868935141	0.66708048	0.986332239	0.381932112	0.981323791	0.875154049	1.188788281	0.894489614	0.8565303	1.338741829	1.022656802	0.54044899	0	0.738462588	1.118828707	0.909520075	0.891976561	1.685998105	1.208476061	0	1.249489358
Isoleucine_13C_6	0.631200892	0.090414433	-0.050855967	-0.097790995	-0.120907397	-0.034292985	0.281121627	-0.002544932	0.037619982	0.198888181	0.342657865	0.099171638	-0.037911743	-0.025131122	0.002215448	0.00649394	-0.003357508	-0.081687489	-0.026405259	-0.075232921	-0.051524621	0	-0.069351832	-0.014227404	-0.008810955	-0.020697948	-0.150234303	-0.060214373	0	-0.115152521
Serine	101.5154132	105.5089008	102.7568977	106.8310101	100.5660028	99.78460371	101.2868614	102.3184569	100.9134759	101.1424005	103.5167351	99.19348573	102.42884	103.0371456	104.3780818	107.7952236	104.171074	104.345086	104.5321842	101.4727838	102.1567318	0	102.8440766	101.9328942	102.344812	104.9206097	112.64239	103.4570228	0	102.2262471
Serine_13C_1	-0.71792468	-2.544466954	-1.52052433	-1.774035915	1.361956416	2.067420451	2.329299381	-0.498534477	3.129852595	-0.018669973	1.074290594	4.894568269	0.991136524	-1.458951881	-1.728614497	-5.373354597	-1.96630987	-1.941487092	0.428894504	1.834747035	0.667610349	0	-1.384810769	0.836487078	1.644150192	-2.258012123	-4.676350843	0.394942092	0	0.876226961
Serine_13C_2	-3.127375172	-3.263361631	-1.175279196	-5.042778442	-2.540834668	-2.436332254	-2.940317917	-1.789185508	-4.803484875	-1.19148374	-4.962757687	-3.271425326	-2.827503523	-1.984685003	-3.257026394	-2.55426608	-2.900088025	-2.942812297	-5.909706205	-3.400644033	-3.342407784	0	-2.065395248	-2.061787955	-3.857889279	-3.011765623	-8.795341381	-3.930325385	0	-3.04174704
Serine_13C_3	2.329886675	0.298927765	-0.061094131	-0.014195782	0.612875484	0.584308091	-0.675842815	-0.030736892	0.76015643	0.067753195	0.371731986	-0.816628677	-0.592473031	0.406491265	0.607559128	0.132397055	0.695323881	0.539213424	0.948627527	0.093113214	0.518065631	0	0.606129423	-0.707593342	-0.13107291	0.349168091	0.8293022	0.078360502	0	-0.060726982
Glycine	98.71711475	108.004888	117.3179427	107.9714457	0	107.560433	0	121.873843	0	103.0790483	105.5093737	0	0	100.8613032	104.3187169	100.107439	100.7952682	102.9022176	113.1908016	117.3834214	104.0608575	0	96.69202273	118.8051046	99.50104119	97.27012135	0	0	0	101.5808253
Glycine_13C_1	0.163619623	-5.548538196	-7.505098805	-0.879404461	0	-5.937378067	0	-14.22103263	0	-5.23764873	1.41961156	0	0	0.391127912	0.954236564	1.222836849	1.507608676	1.140603403	-7.013865353	-11.90647945	1.969783552	0	2.588955455	-15.87759738	2.884070232	4.298420241	0	0	0	-0.36062279
Glycine_13C_2	1.119265626	-2.456349833	-9.812843848	-7.092041268	0	-1.623054939	0	-7.6528104	0	2.158600408	-6.928985266	0	0	-1.252431098	-5.272953428	-1.330275815	-2.30287683	-4.042821048	-6.176936268	-5.476941904	-6.030641077	0	0.719021816	-2.927507182	-2.385111422	-1.568541591	0	0	0	-1.220202508
Fumaric acid	81.56300713	71.26757919	77.56558178	92.71515882	77.42151365	55.77200326	66.54226198	63.02341853	89.5394271	69.48937696	80.33206215	66.66199929	85.05387698	64.71336117	59.70653845	76.37662346	74.06598433	67.15910229	75.34728074	63.4911913	56.96116072	82.15704318	57.81521089	65.74437905	71.78362807	77.77413853	80.9563996	60.89219998	61.37988647	81.07437205
Fumaric acid_13C_1	7.390014683	-0.639393956	-0.032560839	-9.313019716	-0.335804346	4.38548958	8.959511498	5.5812103	4.097866277	10.38820683	-1.652418177	-6.877113282	2.44969634	2.523520871	16.32226939	4.75924643	3.063558142	4.917293928	-0.947588897	2.458558028	11.94014641	2.276089413	6.812234169	-1.288376567	0.153620624	3.524069189	-13.78470531	3.901640949	0.170693364	-0.101793894
Fumaric acid_13C_2	16.18170686	11.00939213	20.24812303	10.51773279	17.34461129	27.1707465	19.60513383	22.27600115	-0.617127473	11.35127492	17.33245319	29.34221171	-0.296950569	26.74366146	13.34157114	18.29377383	20.41974359	25.31568526	19.51994607	22.75916732	18.79719956	12.77475568	27.08588405	24.43056756	26.25060283	17.68260657	42.14535733	21.08958719	29.11752518	16.82590565
Fumaric acid_13C_3	-4.196115962	-2.51782076	4.99313391	8.559339465	8.724181081	11.90691616	8.226378542	6.151376713	8.630169317	12.06233934	6.808780848	16.26423548	15.63920214	2.23848154	14.55481198	2.855480599	5.318055869	6.022866476	9.554373209	16.18242734	13.64607834	4.942010584	6.878963891	16.10454405	-1.511933544	3.321648402	-6.774544342	9.896288076	10.61785078	4.622692895
Fumaric acid_13C_4	-0.938612708	20.88024339	-2.774277881	-2.479211354	-3.154501679	0.764844496	-3.333285851	2.967993305	-1.650335224	-3.291198053	-2.820878013	-5.391333209	-2.845824898	3.780974958	-3.925190958	-2.285124328	-2.867341933	-3.414947957	-3.474011123	-4.891343989	-1.344585029	-2.149898853	1.407706993	-4.991114082	3.324082029	-2.302462688	-2.542507278	4.2202838	-1.285955784	-2.421176702
Asparatic acid	71.67503376	70.87580693	0	69.55266774	0	59.20422824	0	56.628093	71.63247659	66.37484913	69.38087812	0	0	58.74361949	60.3932639	70.11974111	68.70032683	65.15347446	68.91486019	57.84235616	61.9458018	0	59.95966036	63.12232842	64.90282891	64.64924315	57.88915467	0	0	67.29461489
Asparatic acid_13C_1	13.56663118	14.2663441	0	15.36635049	0	17.64296657	0	18.60532672	14.94660074	15.20047928	14.70366671	0	0	13.18248566	14.36172365	15.19962997	14.41084814	16.35715616	14.53354779	18.22723488	15.26868264	0	19.99202112	17.71202966	16.80472069	17.75537255	19.38933891	0	0	16.10481141
Asparatic acid_13C_2	12.46486722	13.53341187	0	13.71493786	0	19.8436988	0	19.96313425	11.69792486	16.66768786	15.99584784	0	0	25.25227727	19.62355237	12.94851032	14.82974225	16.11301879	15.82677327	20.19259759	18.19717448	0	17.95386191	16.85848714	15.13768989	14.19711532	19.04239974	0	0	13.31792135
Asparatic acid_13C_3	4.45598149	2.692333431	0	3.481623967	0	4.407857211	0	7.531096168	3.700752189	4.257200127	1.46148634	0	0	6.410311403	8.20669923	2.940144975	3.723941951	4.155881612	2.916672232	5.814406502	6.535947712	0	4.256253347	4.525525922	4.721649931	4.768603143	6.865423312	0	0	4.599003382
Asparatic acid_13C_4	-2.162513654	-1.367896339	0	-2.115580063	0	-1.098750831	0	-2.727650138	-1.97775437	-2.500216395	-1.541879011	0	0	-3.588693817	-2.585239152	-1.208026376	-1.664859178	-1.779531027	-2.191853478	-2.076595133	-1.947606638	0	-2.161796737	-2.218371145	-1.566889424	-1.370334159	-3.186316633	0	0	-1.316351029
Pyroglutamic acid	83.49582698	87.56410165	85.81384007	0	73.84660231	0	85.11041417	84.13149907	96.9888751	91.54387528	93.43547114	86.55952555	90.3240664	89.60089582	94.94296955	86.94650723	81.51662545	0	0	82.84602981	78.56455643	74.29836423	80.32017759	86.47961618	85.07285331	81.90916236	85.57312725	85.58185173	85.24452701	89.70713531
Pyroglutamic acid_13C_1	2.919125301	5.74061286	7.081739498	0	5.722717278	0	3.3683239	4.385837353	2.24535341	1.560682457	2.032279302	7.249817278	3.805374708	3.962881666	3.208900138	4.363825681	4.829156449	0	0	4.564410222	3.714755006	3.862562717	6.6310251	5.006678752	4.368210389	4.819925402	-1.593383742	2.661703356	4.242707922	6.011219023
Pyroglutamic acid_13C_2	4.562776203	2.845152242	7.5791923	0	16.61811941	0	7.239509633	6.078403351	0.646896541	8.584709744	2.05300167	8.679432831	8.913308171	3.94340886	1.043024078	8.270712772	8.302621368	0	0	7.796422713	8.579762243	11.58510935	8.625078092	5.5262584	7.908556983	9.929460704	14.17221771	6.957334499	6.792647327	4.150350347
Pyroglutamic acid_13C_3	2.358341697	5.570822091	-0.741184697	0	2.775381955	0	3.959512536	3.715747529	0.479238004	-1.061867059	1.817916817	-2.972915405	-2.756517734	2.312736209	0.315240365	-0.474774429	4.201556275	0	0	2.056219823	5.863932953	4.331985372	3.460406278	3.936988019	1.508760973	3.963567185	2.435586252	2.290448853	1.725958143	0.0142871
Pyroglutamic acid_13C_4	-0.996624102	-1.444586036	0.367948198	0	0.171953368	0	0.907759152	1.978887741	-0.356437938	-0.747773105	1.034036241	0.414642805	-0.500563191	0.528931473	0.662487054	0.853345174	1.337244424	0	0	2.962670372	3.548308033	6.680065695	1.031006352	-0.650156065	0.774127102	-0.20024772	-0.281075074	1.653594129	2.172895497	0.087808307
Pyroglutamic acid_13C_5	7.66055392	-0.276102809	-0.10153537	0	0.865225679	0	-0.585519393	-0.290375043	-0.003925116	0.120372683	-0.372705171	0.069496941	0.214331642	-0.348854031	-0.17262119	0.040383577	-0.187203971	0	0	-0.225752936	-0.271314663	-0.758087367	-0.067693412	-0.299385282	0.367491244	-0.421867936	-0.306472397	0.85506743	-0.178735895	0.029199912
Glutamatic acid	55.94960516	49.4534222	57.44484697	74.78942588	0	43.94385106	0	44.61920968	77.99879356	49.5020371	57.36022365	0	0	52.02104583	43.94299703	51.81181642	46.21968017	52.44124278	48.90199637	53.56035098	50.10468205	0	50.87390145	0	51.35707375	51.39721401	0	0	0	52.64427807
Glutamatic acid_13C_1	10.37142106	15.80212885	14.80615827	-1.953248243	0	11.31762495	0	11.48268316	-3.352720828	12.78597077	12.50438499	0	0	10.092284	13.34565418	12.29604759	12.96642974	10.8850487	11.7648295	-0.168350168	12.2320595	0	12.97788358	0	14.32822001	14.24454763	0	0	0	9.563881441
Glutamatic acid_13C_2	23.51246469	19.33487282	32.25948866	20.16826808	0	26.31665956	0	24.58733266	20.08802568	24.34952818	17.78951174	0	0	22.35382871	26.77519502	22.57684544	26.27880515	21.48204327	21.84793199	37.38598102	22.8957374	0	19.94240711	0	22.91236266	20.25544232	0	0	0	25.91980146
Glutamatic acid_13C_3	9.128074074	13.03106006	-2.057661261	11.43266887	0	12.05300232	0	16.66284613	9.161894265	10.3662254	10.95333507	0	0	14.9538483	12.02044487	10.56651133	12.13454238	12.40036334	15.54236317	5.436179982	11.2682269	0	13.93598595	0	9.17658851	11.80461919	0	0	0	10.65893129
Glutamatic acid_13C_4	2.554304192	4.553073742	-2.740230004	-3.905062383	0	6.727193273	0	3.785959612	-3.494589623	1.7918052	3.112107314	0	0	2.599214757	4.307179923	2.678406717	3.134277166	5.000195386	4.311491069	5.634118967	5.758460033	0	4.517492707	0	2.163323018	3.279261895	0	0	0	2.954958464
Glutamatic acid_13C_5	-1.515869167	-2.174557668	0.287397366	-0.532052201	0	-0.358331153	0	-1.138031227	-0.401403049	1.204433354	-1.71956277	0	0	-2.02022161	-0.391471025	0.0703725	-0.733734603	-2.208893472	-2.368612093	-1.848280788	-2.259165881	0	-2.247670797	0	0.062432044	-0.981085047	0	0	0	-1.741850726
Citric acid	67.74204978	40.26285324	43.48395931	41.76954897	31.58715775	28.71299122	45.49139185	39.60233121	54.73390277	49.95122381	71.69781933	51.27326294	46.81478844	39.53035036	47.14303172	58.8372589	42.45186176	35.26143306	36.23985295	36.64218109	32.06068706	33.26227571	32.6520809	43.97928607	47.26520503	45.08578877	41.38292662	27.28814296	0	39.30682324
Citric acid_13C_1	4.273924469	9.84286539	8.729842825	6.481335376	9.0801078	5.292402163	5.087132604	1.363479995	-0.433972583	2.947923576	-6.548178987	5.300021374	-2.358473146	4.110907393	4.54508559	-0.744251373	3.875406486	7.621494528	6.462556845	3.70095607	6.185950345	6.988804713	5.100073356	5.077373497	3.383679874	2.962500865	3.804799678	7.046902698	0	6.308068023
Citric acid_13C_2	25.06850326	32.56897026	34.21922841	41.21537272	42.9243448	43.92270385	33.82984474	41.51784155	38.76629065	40.79904876	32.64756673	35.00892614	44.4249235	37.2351322	34.14759241	32.75772305	37.03970463	43.3141438	45.51032768	39.3831324	38.59142434	38.74140087	43.54991509	39.66345866	36.53490817	40.01306759	36.22744036	44.82020602	0	37.20951812
Citric acid_13C_3	1.304514719	10.94554319	10.36784718	5.703351423	5.864547123	13.24906261	10.19603763	9.16937441	-1.023792903	2.011233871	-0.77542761	4.818578675	5.807876965	9.956976935	8.778156473	7.235070484	10.06123313	7.317582007	6.004292575	13.84401146	10.40504921	9.898094917	8.910998248	10.1521094	11.24591593	6.233963501	9.941433849	7.069264908	0	11.21078422
Citric acid_13C_4	3.136238817	8.341645735	6.668197591	7.117904017	12.67187439	6.098919511	8.343987164	9.138467162	13.22660394	8.091910092	5.615391367	8.904614069	8.927798882	8.513479938	6.073761418	2.080977138	8.896212351	6.807051572	6.610565685	6.214262544	12.90619233	9.949932349	8.306175433	2.806083097	1.4950482	6.140556454	12.22818419	12.99525052	0	7.155224498
Citric acid_13C_5	-0.630997726	-0.221034305	-1.636898687	-1.753709655	0.651329922	4.622587467	-0.373456088	2.020662168	-3.13540745	-2.191925972	-1.586826754	-4.137854681	-1.322807851	0.691845455	2.265897542	0.238769312	-0.580207269	3.144188354	2.26688342	4.154134364	1.934963674	3.650428458	2.045961991	-0.003436868	0.903138186	2.604586011	-2.053329038	3.378232788	0	-0.250675835
Citric acid_13C_6	-0.894233324	-1.740843512	-1.832176635	-0.533802853	-2.779361794	-1.898666824	-2.5749379	-2.812156493	-2.133624427	-1.609414139	-1.050344078	-1.167548517	-2.294106785	-0.03869228	-2.953525151	-0.405547508	-1.744211088	-3.465893322	-3.094479153	-3.938677932	-2.084266953	-2.490937013	-0.565205017	-1.674873855	-0.827895388	-3.040463181	-1.531455656	-2.597999895	0	-0.939742258
Urea	100.0452885	93.12513553	90.64811566	92.42939774	93.22676928	91.30935616	92.07389472	91.492632	101.1804975	96.41649805	96.36193662	100.1163032	95.64155789	93.80108271	91.87947873	93.87729884	96.58247235	90.78805866	92.51539416	90.76750932	92.37657214	93.11003746	91.83454811	92.39316849	94.53764465	91.39587582	95.89081932	95.15296134	88.41080152	89.67285627
Urea_13C_1	-0.04528847	6.874864466	9.351884342	7.570602255	6.773230718	8.690643836	7.926105277	8.507367998	-1.180497484	3.583501947	3.638063383	-0.116303163	4.358442113	6.198917291	8.120521268	6.122701156	3.417527651	9.21194134	7.484605841	9.232490676	7.623427856	6.889962542	8.165451893	7.606831511	5.462355353	8.604124176	4.109180681	4.847038656	11.58919848	10.32714373
Ethanolamine	112.0852779	112.2397261	110.8229425	111.2200226	111.7355842	111.5140925	111.090961	111.6558372	111.3584295	111.2431896	112.1622569	111.7141994	110.0909956	111.5171265	110.1795207	110.9897587	109.2637733	111.6963814	111.9581174	111.9165457	112.1613838	112.1998764	111.7110452	112.3971408	111.4059187	111.6987614	111.5640464	111.1397655	109.1309631	111.6000927
Ethanolamine_13C_1	-8.808460423	-8.619972963	-7.496510539	-8.047968081	-8.650411459	-8.168818851	-8.220912604	-8.508679089	-8.670129543	-8.190107973	-8.819988378	-9.102679667	-6.999986438	-8.308522417	-7.230864216	-7.807267886	-6.798201511	-8.427787255	-8.59807054	-8.670736359	-8.988279622	-8.713518975	-8.284277035	-9.378935325	-8.191760715	-8.158086761	-8.294283697	-7.479576834	-6.736791112	-8.453585505
Ethanolamine_13C_2	-3.276817524	-3.619753163	-3.326431929	-3.172054472	-3.085172739	-3.345273685	-2.870048389	-3.147158137	-2.688299962	-3.053081628	-3.342268526	-2.611519781	-3.091009205	-3.208604105	-2.94865651	-3.182490852	-2.465571788	-3.268594165	-3.360046876	-3.245809361	-3.173104161	-3.486357388	-3.42676812	-3.018205451	-3.214157996	-3.540674677	-3.269762698	-3.66018871	-2.394171984	-3.146507181
Glyoxylic acid	0	99.03304712	99.34219351	108.1321663	96.02341333	96.7210309	99.33014753	95.17383181	109.2068269	101.8331573	104.675082	99.70004272	96.5100926	100.5855224	99.11158218	100.4909753	99.95382564	94.039535	99.52151454	94.23852406	97.12171689	95.10866261	100.2484722	101.1624016	101.1940824	97.26484914	100.7472694	99.55827629	95.07011642	96.91235853
Glyoxylic acid_13C_1	0	5.586940858	5.26301082	-3.946883609	5.271805673	6.614529273	3.961614471	7.65333181	-5.072664634	2.653003619	-0.324581164	4.887909518	6.286569632	3.960198202	5.504633999	4.059327248	4.622150684	7.284490259	2.581681382	9.181192831	3.400577112	8.121200608	3.228238437	2.103796587	1.061858824	5.33930767	-0.203222967	3.205380071	8.573584174	3.754656219
Glyoxylic acid_13C_2	0	-4.619987976	-4.605204328	-4.185282699	-1.295219003	-3.335560169	-3.291761997	-2.827163616	-4.134162278	-4.486160931	-4.350500787	-4.587952241	-2.796662236	-4.5457206	-4.616216178	-4.550302533	-4.575976328	-1.324025263	-2.103195918	-3.419716893	-0.522294003	-3.229863222	-3.476710608	-3.266198155	-2.255941197	-2.604156815	-0.544046473	-2.763656357	-3.643700597	-0.667014745
Malic acid	117.0438346	76.50712106	79.56391139	87.38004252	82.64397606	73.25577967	68.36825597	69.05601473	122.8189112	89.09022888	89.49796554	72.90599301	75.53358193	67.52289794	72.03483839	86.73494442	77.70848946	67.59372198	75.92346489	75.02639427	68.27187827	69.67450165	67.92535941	72.45174433	63.23458727	76.82550638	92.89058589	73.19084831	71.94290433	75.84311121
Malic acid_13C_1	-4.564623426	4.95422177	8.048119447	12.7700839	16.65576558	8.013387591	14.79357374	9.310428084	-31.32236441	-22.72029622	14.42220911	16.86467247	12.0648425	21.20953604	12.40800725	1.842429605	15.56745798	18.86021447	17.75038027	12.67580127	13.01180631	18.18661262	15.44486474	19.50866955	21.31346606	19.53543848	-1.796248491	5.862644034	9.884687979	9.079403734
Malic acid_13C_2	-15.08374911	24.68362157	13.61003483	5.489311573	-8.219553274	24.34178378	6.756043528	17.88894753	11.27996141	19.83673234	0.268235745	21.19484745	17.55677996	10.64976704	16.63919826	6.989758338	6.936489669	16.2329592	15.66194327	8.699706388	18.87016807	15.95779517	12.53269242	18.42085801	14.28792785	12.03331184	16.40279155	19.91465006	9.127344579	18.46579588
Malic acid_13C_3	1.565098598	-2.808240081	1.867343744	-5.349241466	3.733484858	-2.081227041	15.89050214	9.280668853	-1.58820841	22.23874297	-4.299839159	-9.562672488	-2.578379871	4.118816151	2.698770894	8.080046869	2.214029547	0.645270517	-8.349478291	2.352750784	4.347275448	-0.929305882	8.950979259	-9.210765166	5.495648764	-7.694356907	-6.247607456	5.938219542	14.80771499	-0.134307431
Malic acid_13C_4	1.039439297	-3.336724313	-3.089409416	-0.290196529	5.186326771	-3.529723992	-5.808375383	-5.536059204	-1.188299817	-8.445407977	0.111428759	-1.402840439	-2.576824522	-3.501017165	-3.780814797	-3.647179228	-2.426466652	-3.332166177	-0.986310143	1.245347287	-4.501128096	-2.889603563	-4.853895836	-1.170506727	-4.331629943	-0.699899798	-1.249521491	-4.906361946	-5.762651882	-3.254003395
Phenylalanine	104.2988898	104.2830198	102.5126978	102.33804	96.07785186	101.5376718	97.95188384	101.2929632	102.3560445	103.1696187	101.1708835	100.4789414	99.89202253	103.3684452	102.2991705	100.7252814	102.9427062	103.0179721	103.2678523	97.67234709	101.0712013	104.0363725	101.4141166	99.62368108	100.1197312	101.8441902	103.2591071	100.5417442	0	101.0642247
Phenylalanine_13C_1	-0.78540551	-1.208427357	-0.278154348	-0.834293475	1.715054348	0.910764278	1.501205981	0.48811343	0.853942713	-0.603285336	0.195659784	0.891805346	0.882465488	-1.599876181	0.987218509	1.293586672	-0.274266152	-0.37867345	-0.004611382	1.374105337	0.852320296	-3.048720131	1.359544405	0.564005839	1.403316789	0.426049651	-1.184668844	0.20535546	0	1.00516074
Phenylalanine_13C_2	-4.116466124	-3.919708005	-4.090347256	-4.033382849	-3.558995121	-4.051558335	-4.067189958	-4.002676557	-4.185818348	-4.087514267	-4.079064427	-4.113838567	-4.089436518	-4.005931311	-3.853171286	-3.848609031	-4.03007394	-4.101606231	-4.145260773	-4.044528125	-3.987075687	-3.902531456	-4.064749745	-4.050053723	-4.145400108	-3.966460659	-4.038836408	-3.91647714	0	-3.89689663
Phenylalanine_13C_3	0.223455124	0.22277252	0.203792763	0.221268535	0.087020888	0.154236873	0.13803282	0.167232519	0.167170141	0.215459049	0.186049775	0.162396356	0.161596642	0.247796977	0.204185439	0.122011798	0.197479967	0.207966885	0.196448603	0.141602512	0.151586741	0.295539196	0.137614045	0.171293624	0.145320046	0.165517619	0.234252234	0.172114468	0	0.137348934
Phenylalanine_13C_4	0.129051319	0.184271655	0.129216481	0.126326743	0.116045537	0.130241789	0.131925998	0.127879077	0.134449455	0.128494711	0.341779971	0.132218766	0.131427456	0.123978372	0.163452496	0.209495286	0.305649435	0.129380451	0.131480177	0.130961075	0.128065481	0.117932866	0.146146338	0.129565225	0.134207945	0.126587221	0.125809844	0.124586565	0	0.20391453
Phenylalanine_13C_5	-0.013992622	-0.019186206	-0.013326504	-0.013794566	-0.008649027	-0.011686581	-0.011234687	-0.01201522	-0.012354256	-0.013691123	-0.03180913	-0.012083823	-0.012027359	-0.014558672	-0.01703438	-0.017928561	-0.029036107	-0.013476834	-0.013201941	-0.011321401	-0.011490818	-0.015837507	-0.012502521	-0.012249539	-0.011595235	-0.011882087	-0.014171843	-0.012003691	0	-0.017913725
Phenylalanine_13C_6	-0.003618782	-0.005395026	-0.003665172	0.14400971	0.891168176	0.086957813	0.587187235	0.034110675	0.485796224	0.051413118	-0.010498935	-0.003836134	-0.003796345	-0.003414997	-0.004747468	-0.006374138	-0.009334329	-0.00365353	-0.003737451	0.586298997	-0.003713883	-0.003181642	0.132805383	-0.00372575	-0.003916843	0.29746094	-0.003473491	0.37164436	0	-0.006178757
Phenylalanine_13C_7	0.208423262	0.341498117	0.626974439	1.718395516	1.491293932	0.490771407	1.765151211	0.695784553	0.177353357	0.535096308	1.194331921	1.927178021	2.325513422	1.001772403	0.02160458	0.092684535	0.470395813	0.438053974	0.289196889	2.121691805	1.219661424	0.702153053	0.561109218	1.724622373	1.616361981	0.874735877	1.092482393	1.899084714	0	0.998390566
Phenylalanine_13C_8	-0.018576412	-0.030466714	0.42333503	0.013053918	0.661093439	0.037389632	-0.182225699	0.322502115	0.034478196	0.102731027	0.208104745	-0.173041629	-0.035880502	0.140234556	0.068397884	0.317637624	0.121364403	0.077932494	0.122536327	0.972314584	-0.089180808	-0.062996513	0.097073325	0.542123874	0.176102634	0.082653097	-0.022091403	-0.035373116	0	0.21845095
Phenylalanine_13C_9	0.078239914	0.15162124	0.489476816	0.320376471	2.528115971	0.715211305	2.18526326	0.886106169	-0.01106197	0.501677781	0.824562799	0.710260285	0.748115182	0.741553624	0.130923754	1.112214416	0.30511475	0.626104144	0.159297225	1.056528131	0.668625925	1.881269602	0.228842996	1.310736993	0.565871634	0.161148168	0.551590373	0.649324159	0	0.293498719
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	Quantified m/z	PubChem ID	KEGG ID	HMDB
Pyruvic acid	174	1060	C00022	HMDB0000243
Pyruvic acid_13C_1	175	1060	C00022	HMDB0000243
Pyruvic acid_13C_2	176	1060	C00022	HMDB0000243
Pyruvic acid_13C_3	177	1060	C00022	HMDB0000243
Lactic acid	219	107689	C00186	HMDB0000190
Lactic acid_13C_1	220	107689	C00186	HMDB0000190
Lactic acid_13C_2	221	107689	C00186	HMDB0000190
Lactic acid_13C_3	222	107689	C00186	HMDB0000190
beta-Alanine	116	239	C00099	HMDB0000056
beta-Alanine_13C_1	117	239	C00099	HMDB0000056
beta-Alanine_13C_2	118	239	C00099	HMDB0000056
beta-Alanine_13C_3	119	239	C00099	HMDB0000056
Leucine	86	6106	C00123	HMDB0000687
Leucine_13C_1	87	6106	C00123	HMDB0000687
Leucine_13C_2	88	6106	C00123	HMDB0000687
Leucine_13C_3	89	6106	C00123	HMDB0000687
Leucine_13C_4	90	6106	C00123	HMDB0000687
Leucine_13C_5	91	6106	C00123	HMDB0000687
Leucine_13C_6	92	6106	C00123	HMDB0000687
Isoleucine	86	6306	C00407	HMDB0000172
Isoleucine_13C_1	87	6306	C00407	HMDB0000172
Isoleucine_13C_2	88	6306	C00407	HMDB0000172
Isoleucine_13C_3	89	6306	C00407	HMDB0000172
Isoleucine_13C_4	90	6306	C00407	HMDB0000172
Isoleucine_13C_5	91	6306	C00407	HMDB0000172
Isoleucine_13C_6	92	6306	C00407	HMDB0000172
Serine	116	5951	C00716	HMDB0062263
Serine_13C_1	117	5951	C00716	HMDB0062263
Serine_13C_2	118	5951	C00716	HMDB0062263
Serine_13C_3	119	5951	C00716	HMDB0062263
Glycine	276	750	C00037	HMDB0000123
Glycine_13C_1	277	750	C00037	HMDB0000123
Glycine_13C_2	278	750	C00037	HMDB0000123
Fumaric acid	245	444972	C00122	HMDB0000134
Fumaric acid_13C_1	246	444972	C00122	HMDB0000134
Fumaric acid_13C_2	247	444972	C00122	HMDB0000134
Fumaric acid_13C_3	248	444972	C00122	HMDB0000134
Fumaric acid_13C_4	249	444972	C00122	HMDB0000134
Asparatic acid	160	5960	C00049	HMDB0000191
Asparatic acid_13C_1	161	5960	C00049	HMDB0000191
Asparatic acid_13C_2	162	5960	C00049	HMDB0000191
Asparatic acid_13C_3	163	5960	C00049	HMDB0000191
Asparatic acid_13C_4	164	5960	C00049	HMDB0000191
Pyroglutamic acid	258	7405	C01879	HMDB0000267
Pyroglutamic acid_13C_1	259	7405	C01879	HMDB0000267
Pyroglutamic acid_13C_2	260	7405	C01879	HMDB0000267
Pyroglutamic acid_13C_3	261	7405	C01879	HMDB0000267
Pyroglutamic acid_13C_4	262	7405	C01879	HMDB0000267
Pyroglutamic acid_13C_5	263	7405	C01879	HMDB0000267
Glutamatic acid	246	33032	C00025	HMDB0000148
Glutamatic acid_13C_1	247	33032	C00025	HMDB0000148
Glutamatic acid_13C_2	248	33032	C00025	HMDB0000148
Glutamatic acid_13C_3	249	33032	C00025	HMDB0000148
Glutamatic acid_13C_4	250	33032	C00025	HMDB0000148
Glutamatic acid_13C_5	251	33032	C00025	HMDB0000148
Citric acid	273	311	C00158	HMDB0000094
Citric acid_13C_1	274	311	C00158	HMDB0000094
Citric acid_13C_2	275	311	C00158	HMDB0000094
Citric acid_13C_3	276	311	C00158	HMDB0000094
Citric acid_13C_4	277	311	C00158	HMDB0000094
Citric acid_13C_5	278	311	C00158	HMDB0000094
Citric acid_13C_6	279	311	C00158	HMDB0000094
Urea	189	1176	C00086	HMDB0000294
Urea_13C_1	190	1176	C00086	HMDB0000294
Ethanolamine	174	700	C00189	HMDB0000149
Ethanolamine_13C_1	175	700	C00189	HMDB0000149
Ethanolamine_13C_2	176	700	C00189	HMDB0000149
Glyoxylic acid	134	760	C00048	HMDB0000119
Glyoxylic acid_13C_1	135	760	C00048	HMDB0000119
Glyoxylic acid_13C_2	136	760	C00048	HMDB0000119
Malic acid	233	525	C03668	HMDB0000744
Malic acid_13C_1	234	525	C03668	HMDB0000744
Malic acid_13C_2	235	525	C03668	HMDB0000744
Malic acid_13C_3	236	525	C03668	HMDB0000744
Malic acid_13C_4	237	525	C03668	HMDB0000744
Phenylalanine	120	6140	C00079	HMDB0000159
Phenylalanine_13C_1	121	6140	C00079	HMDB0000159
Phenylalanine_13C_2	122	6140	C00079	HMDB0000159
Phenylalanine_13C_3	123	6140	C00079	HMDB0000159
Phenylalanine_13C_4	124	6140	C00079	HMDB0000159
Phenylalanine_13C_5	125	6140	C00079	HMDB0000159
Phenylalanine_13C_6	126	6140	C00079	HMDB0000159
Phenylalanine_13C_7	127	6140	C00079	HMDB0000159
Phenylalanine_13C_8	128	6140	C00079	HMDB0000159
Phenylalanine_13C_9	129	6140	C00079	HMDB0000159
METABOLITES_END
#END