#METABOLOMICS WORKBENCH silviaradenkovic_20241103_092902 DATATRACK_ID:5339 STUDY_ID:ST003555 ANALYSIS_ID:AN005844 PROJECT_ID:PR002189
VERSION             	1
CREATED_ON             	November 7, 2024, 6:57 am
#PROJECT
PR:PROJECT_TITLE                 	Mitochondrial dysfunction is a driver of cardiac complications in PGM1-CDG with
PR:PROJECT_TITLE                 	implications for therapy
PR:PROJECT_SUMMARY               	Phosphoglucomutase 1 (PGM1) plays a crucial role in linking glycolysis, glycogen
PR:PROJECT_SUMMARY               	metabolism, and glycosylation. Pathogenic variants in PGM1 cause a complex
PR:PROJECT_SUMMARY               	multisystem disease, associated with congenital disorder of glycosylation
PR:PROJECT_SUMMARY               	(PGM1-CDG) and lethal cardiac complications. While treatments exist for the
PR:PROJECT_SUMMARY               	glycosylation defect in PGM1-CDG, the cardiac symptoms persist. To investigate
PR:PROJECT_SUMMARY               	the cardiac-specific impact of PGM1 deficiency, we developed human-induced
PR:PROJECT_SUMMARY               	pluripotent stem cell-derived cardiomyocytes (iCMs) from PGM1-CDG individuals.
PR:INSTITUTE                     	Mayo Clinic
PR:LAST_NAME                     	Radenkovic
PR:FIRST_NAME                    	Silvia
PR:ADDRESS                       	200 2nd Ave SW Rochester MN
PR:EMAIL                         	silradenkovic@gmail.com
PR:PHONE                         	507(77) 6-6107
PR:FUNDING_SOURCE                	NIH
#STUDY
ST:STUDY_TITLE                   	Mitochondrial dysfunction is a driver of cardiac complications in PGM1-CDG with
ST:STUDY_TITLE                   	implications for therapy
ST:STUDY_SUMMARY                 	Phosphoglucomutase 1 (PGM1) plays a crucial role in linking glycolysis, glycogen
ST:STUDY_SUMMARY                 	metabolism, and glycosylation. Pathogenic variants in PGM1 cause a complex
ST:STUDY_SUMMARY                 	multisystem disease, associated with congenital disorder of glycosylation
ST:STUDY_SUMMARY                 	(PGM1-CDG) and lethal cardiac complications. While treatments exist for the
ST:STUDY_SUMMARY                 	glycosylation defect in PGM1-CDG, the cardiac symptoms persist. To investigate
ST:STUDY_SUMMARY                 	the cardiac-specific impact of PGM1 deficiency, we developed human-induced
ST:STUDY_SUMMARY                 	pluripotent stem cell-derived cardiomyocytes (iCMs) from PGM1-CDG individuals.
ST:STUDY_SUMMARY                 	By leveraging omics technologies, we report on significantly reduced beating
ST:STUDY_SUMMARY                 	capacity and widespread molecular alterations linked to mitochondrial
ST:STUDY_SUMMARY                 	dysfunction and energy failure in PGM1-deficient iCMs. Here, we performed tracer
ST:STUDY_SUMMARY                 	metabolomics experiments to understand metabolic rewiring resulting in cardiac
ST:STUDY_SUMMARY                 	failure in PGM1-CDG. By leveraging omics technologies, we report on
ST:STUDY_SUMMARY                 	significantly reduced beating capacity and widespread molecular alterations
ST:STUDY_SUMMARY                 	linked to mitochondrial dysfunction and energy failure in PGM1-deficient iCMs.
ST:STUDY_SUMMARY                 	Tracer metabolomics showed rewiring of glucose metabolism and depletion of ATP,
ST:STUDY_SUMMARY                 	in line with mitochondrial dysfunction assessed by mitochondrial stress tests.
ST:STUDY_SUMMARY                 	Moreover, in-silico drug repurposing identified candidates for treating the
ST:STUDY_SUMMARY                 	cardiac complications of PGM1 deficiency. Our findings unveil a cardiac-specific
ST:STUDY_SUMMARY                 	pathomechanism in PGM1 deficiency and propose crucially needed therapeutic
ST:STUDY_SUMMARY                 	strategies targeting heart failure in PGM1-CDG.
ST:INSTITUTE                     	Mayo Clinic
ST:LAST_NAME                     	Radenkovic
ST:FIRST_NAME                    	Silvia
ST:ADDRESS                       	200 2nd Ave SW Rochester MN, USA
ST:EMAIL                         	silradenkovic@gmail.com
ST:PHONE                         	507(77) 6-6107
#SUBJECT
SU:SUBJECT_TYPE                  	Cultured cells
SU:SUBJECT_SPECIES               	Homo sapiens
SU:TAXONOMY_ID                   	9606
SU:GENOTYPE_STRAIN               	WT/PGM1 deficient
SU:AGE_OR_AGE_RANGE              	3-25
SU:GENDER                        	Male and female
SU:CELL_STRAIN_DETAILS           	iPSC-derived cardiomyocytes
#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           	P4	CR01	Sample source:iCardiomyocytes | Genotype:PGM1	Weight (microg)=618,6975; volume (microL)=160; IS (AUC)=2542337536; RAW_FILE_NAME(Raw file name)=CR01
SUBJECT_SAMPLE_FACTORS           	P4	CR02	Sample source:iCardiomyocytes | Genotype:PGM1	Weight (microg)=530,8425; volume (microL)=160; IS (AUC)=2564192512; RAW_FILE_NAME(Raw file name)=CR02
SUBJECT_SAMPLE_FACTORS           	P4	CR03	Sample source:iCardiomyocytes | Genotype:PGM1	Weight (microg)=624,0085; volume (microL)=160; IS (AUC)=2135243776; RAW_FILE_NAME(Raw file name)=CR03
SUBJECT_SAMPLE_FACTORS           	C1	CR04	Sample source:iCardiomyocytes | Genotype:WT	Weight (microg)=648,3515; volume (microL)=150; IS (AUC)=2071154816; RAW_FILE_NAME(Raw file name)=CR04
SUBJECT_SAMPLE_FACTORS           	C1	CR05	Sample source:iCardiomyocytes | Genotype:WT	Weight (microg)=679,333; volume (microL)=150; IS (AUC)=2625632512; RAW_FILE_NAME(Raw file name)=CR05
SUBJECT_SAMPLE_FACTORS           	C4	CR06	Sample source:iCardiomyocytes | Genotype:WT	Weight (microg)=618,476; volume (microL)=150; IS (AUC)=2504745216; RAW_FILE_NAME(Raw file name)=CR06
SUBJECT_SAMPLE_FACTORS           	C4	CR07	Sample source:iCardiomyocytes | Genotype:WT	Weight (microg)=537,039; volume (microL)=155; IS (AUC)=2444808960; RAW_FILE_NAME(Raw file name)=CR07
SUBJECT_SAMPLE_FACTORS           	PGM1 P1	CR08	Sample source:iCardiomyocytes | Genotype:PGM1	Weight (microg)=616,263; volume (microL)=140; IS (AUC)=2472128768; RAW_FILE_NAME(Raw file name)=CR08
SUBJECT_SAMPLE_FACTORS           	PGM1 P1	CR09	Sample source:iCardiomyocytes | Genotype:PGM1	Weight (microg)=563,594; volume (microL)=150; IS (AUC)=2459918592; RAW_FILE_NAME(Raw file name)=CR09
SUBJECT_SAMPLE_FACTORS           	PGM1 P1	CR10	Sample source:iCardiomyocytes | Genotype:PGM1	Weight (microg)=592,806; volume (microL)=150; IS (AUC)=2599931136; RAW_FILE_NAME(Raw file name)=CR10
SUBJECT_SAMPLE_FACTORS           	P3	CR11	Sample source:iCardiomyocytes | Genotype:PGM1	Weight (microg)=616,263; volume (microL)=160; IS (AUC)=2319642368; RAW_FILE_NAME(Raw file name)=CR11
SUBJECT_SAMPLE_FACTORS           	P3	CR12	Sample source:iCardiomyocytes | Genotype:PGM1	Weight (microg)=594,576; volume (microL)=165; IS (AUC)=2430729472; RAW_FILE_NAME(Raw file name)=CR12
SUBJECT_SAMPLE_FACTORS           	C3	CR13	Sample source:iCardiomyocytes | Genotype:WT	Weight (microg)=435,9055; volume (microL)=150; IS (AUC)=2445635840; RAW_FILE_NAME(Raw file name)=CR13
SUBJECT_SAMPLE_FACTORS           	C3	CR14	Sample source:iCardiomyocytes | Genotype:WT	Weight (microg)=479,5015; volume (microL)=160; IS (AUC)=2490768896; RAW_FILE_NAME(Raw file name)=CR14
SUBJECT_SAMPLE_FACTORS           	Medium C13	CR15	Sample source:iCardiomyocytes | Genotype:Medium	Weight (microg)=1; volume (microL)=160; IS (AUC)=2513797376; RAW_FILE_NAME(Raw file name)=CR15
SUBJECT_SAMPLE_FACTORS           	Medium C12	CR16	Sample source:iCardiomyocytes | Genotype:Medium	Weight (microg)=1; volume (microL)=160; IS (AUC)=2247294976; RAW_FILE_NAME(Raw file name)=CR16
#COLLECTION
CO:COLLECTION_SUMMARY            	iCardiomyocytes were prepared from iPSC according to previously established
CO:COLLECTION_SUMMARY            	protocols. Briefly, iPSC were plated, on day 1 the medium was changed to medium
CO:COLLECTION_SUMMARY            	containing CHIR inhibitor and B27 minus insulin supplement. The next day, medium
CO:COLLECTION_SUMMARY            	without CHIR was added, and the following day as well, to gradually decrease
CO:COLLECTION_SUMMARY            	CHIR concentration. On the 4th day, the medium was changed and medium containing
CO:COLLECTION_SUMMARY            	IWP2 inhibitor was added. After 2 days, the medium was removed and medium
CO:COLLECTION_SUMMARY            	containing no inhibitors was added. Once the beating was observed, medium
CO:COLLECTION_SUMMARY            	containing B27 supplement with insulin was added. Cells were collected at day
CO:COLLECTION_SUMMARY            	15. For metabolomics, cells were replated, and medium containing U-13 glucose or
CO:COLLECTION_SUMMARY            	normal glucose was added and cells were incubated for 48h. iCardiomyocytes were
CO:COLLECTION_SUMMARY            	collected by scraping from the well. Medium was removed, the cells were washed
CO:COLLECTION_SUMMARY            	with ice-cold saline solution, then, extraction buffer containing ice-cold 80%
CO:COLLECTION_SUMMARY            	Methanol and internal standard (d27 myristic acid) was added. Cells were
CO:COLLECTION_SUMMARY            	incubated for 2 min with extraction buffer and then scraped. The cells together
CO:COLLECTION_SUMMARY            	with extraction buffer were transferred to a cold eppendorf and stored at -80C
CO:COLLECTION_SUMMARY            	before further processing.
CO:SAMPLE_TYPE                   	iPSC-derived cardiomyocytes (iCardiomyocytes)
CO:VOLUMEORAMOUNT_COLLECTED      	120-160 microL
CO:STORAGE_CONDITIONS            	-80℃
#TREATMENT
TR:TREATMENT_SUMMARY             	NA
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	Briefly, after collection, the samples were centrifuged at 15,000 rpm, 4 °C,
SP:SAMPLEPREP_SUMMARY            	for 20 min. The liquid phase was transferred to an MS vial and used for LC/MS.
SP:SAMPLEPREP_SUMMARY            	The pellet was used to determine protein content.
SP:PROCESSING_STORAGE_CONDITIONS 	-80℃
SP:EXTRACT_STORAGE               	-80℃
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_SUMMARY        	C18 iP REVERSE PHASE
CH:CHROMATOGRAPHY_TYPE           	Reversed phase
CH:INSTRUMENT_NAME               	Waters Acquity
CH:COLUMN_NAME                   	Waters ACQUITY UPLC HSS T3 (150 x 2.1mm,1.8um)
CH:SOLVENT_A                     	100% water; 10mM tributylamine; 15mM acetic acid
CH:SOLVENT_B                     	100% methanol
CH:FLOW_GRADIENT                 	The gradient started with 5% of solvent B and 95% solvent A and remained at 5% B
CH:FLOW_GRADIENT                 	until 2 min post injection. A linear gradient to 37% B was carried out until 7
CH:FLOW_GRADIENT                 	min and increased to 41% until 14 min. Between 14 and 26 minutes the gradient
CH:FLOW_GRADIENT                 	increased to 95% of B and remained at 95% B for 4 minutes. At 30 min the
CH:FLOW_GRADIENT                 	gradient returned to 5% B. The chromatography was stopped at 40 min
CH:FLOW_RATE                     	0.25 mL/min
CH:COLUMN_TEMPERATURE            	40
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:INSTRUMENT_NAME               	Thermo Q Exactive Orbitrap
MS:INSTRUMENT_TYPE               	Orbitrap
MS:MS_TYPE                       	ESI
MS:ION_MODE                      	NEGATIVE
MS:MS_COMMENTS                   	El-Maven polly, ThermoFisher Xcalibur, Metabolites were annotated based on the
MS:MS_COMMENTS                   	in-house metabolite library- elution time and m/z values
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	AUC
MS_METABOLITE_DATA_START
Samples	CR01	CR02	CR03	CR04	CR05	CR06	CR07	CR08	CR09	CR10	CR11	CR12	CR13	CR14	CR15	CR16
Factors	Sample source:iCardiomyocytes | Genotype:PGM1	Sample source:iCardiomyocytes | Genotype:PGM1	Sample source:iCardiomyocytes | Genotype:PGM1	Sample source:iCardiomyocytes | Genotype:WT	Sample source:iCardiomyocytes | Genotype:WT	Sample source:iCardiomyocytes | Genotype:WT	Sample source:iCardiomyocytes | Genotype:WT	Sample source:iCardiomyocytes | Genotype:PGM1	Sample source:iCardiomyocytes | Genotype:PGM1	Sample source:iCardiomyocytes | Genotype:PGM1	Sample source:iCardiomyocytes | Genotype:PGM1	Sample source:iCardiomyocytes | Genotype:PGM1	Sample source:iCardiomyocytes | Genotype:WT	Sample source:iCardiomyocytes | Genotype:WT	Sample source:iCardiomyocytes | Genotype:Medium	Sample source:iCardiomyocytes | Genotype:Medium
PEP	663E+04	409E+04	544E+04	192E+05	200E+05	247E+05	469E+05	454E+05	392E+05	396E+05	381E+05	369E+05	200E+05	189E+05	000E+00	458E+03
Lactate	852E+08	889E+08	793E+08	763E+08	925E+08	773E+08	488E+08	562E+08	374E+08	742E+08	685E+08	505E+08	702E+08	603E+08	535E+06	443E+06
Hexose-P	276E+07	166E+07	214E+07	297E+06	208E+06	265E+06	803E+06	737E+06	671E+06	501E+06	474E+06	445E+06	537E+06	550E+06	426E+04	443E+04
Hexose	496E+07	320E+07	416E+07	769E+07	648E+07	102E+08	692E+07	551E+07	502E+07	424E+07	383E+07	283E+07	591E+07	555E+07	563E+07	482E+07
Glyceraldehyde-phosphate	169E+06	124E+06	124E+06	141E+06	929E+05	120E+06	128E+06	155E+06	121E+06	239E+06	224E+06	218E+06	212E+06	189E+06	257E+04	334E+04
DHAP	531E+05	266E+05	456E+05	224E+06	151E+06	412E+06	118E+07	132E+07	129E+07	845E+06	756E+06	720E+06	617E+06	533E+06	209E+04	214E+04
Hexose-bisphosphate	832E+05	508E+05	661E+05	214E+06	105E+06	144E+06	850E+06	170E+07	144E+07	118E+07	968E+06	838E+06	320E+06	300E+06	957E+04	788E+04
Hexosamine-phosphate	443E+04	415E+04	330E+04	609E+04	980E+04	960E+04	698E+04	468E+04	502E+04	844E+04	602E+04	837E+04	748E+04	747E+04	748E+03	882E+03
Pyruvate	908E+07	930E+07	722E+07	120E+08	135E+08	105E+08	759E+07	877E+07	428E+07	108E+08	969E+07	460E+07	758E+07	555E+07	262E+07	231E+07
Pentitol	419E+05	401E+05	458E+05	411E+05	551E+05	120E+06	720E+05	645E+05	488E+05	573E+05	494E+05	305E+05	722E+05	501E+05	323E+05	289E+05
Polyol	497E+06	457E+06	419E+06	190E+06	311E+06	868E+06	306E+06	506E+06	497E+06	153E+06	142E+06	162E+06	448E+06	407E+06	523E+04	748E+04
Fumarate	138E+07	142E+07	148E+07	196E+07	211E+07	250E+07	197E+07	215E+07	191E+07	171E+07	156E+07	164E+07	198E+07	172E+07	588E+06	612E+06
(Iso)citrate	960E+07	805E+07	900E+07	137E+08	166E+08	197E+08	132E+08	193E+08	170E+08	162E+08	155E+08	152E+08	191E+08	158E+08	123E+07	124E+07
Malate	263E+08	275E+08	280E+08	363E+08	380E+08	449E+08	359E+08	394E+08	364E+08	320E+08	301E+08	316E+08	376E+08	326E+08	136E+08	135E+08
Oxoglutarate	974E+07	891E+07	898E+07	106E+08	101E+08	111E+08	918E+07	871E+07	847E+07	107E+08	102E+08	106E+08	109E+08	101E+08	896E+07	871E+07
Succinate	416E+07	414E+07	416E+07	517E+07	765E+07	586E+07	452E+07	471E+07	401E+07	539E+07	505E+07	508E+07	781E+07	667E+07	236E+07	244E+07
Aconitate	761E+06	763E+06	780E+06	904E+06	916E+06	101E+07	888E+06	854E+06	795E+06	926E+06	890E+06	822E+06	990E+06	874E+06	433E+06	467E+06
Glutamate	234E+08	226E+08	217E+08	294E+08	322E+08	300E+08	261E+08	260E+08	251E+08	289E+08	274E+08	279E+08	297E+08	262E+08	947E+06	102E+07
Glutamine	402E+08	401E+08	433E+08	343E+08	313E+08	278E+08	190E+08	207E+08	185E+08	137E+08	129E+08	137E+08	261E+08	239E+08	490E+07	545E+07
Methionine	409E+06	396E+06	488E+06	520E+06	656E+06	460E+06	335E+06	336E+06	225E+06	574E+06	573E+06	481E+06	369E+06	406E+06	150E+06	155E+06
Phenylalanine	148E+07	164E+07	186E+07	140E+07	265E+07	188E+07	151E+07	121E+07	103E+07	245E+07	232E+07	188E+07	159E+07	154E+07	658E+06	668E+06
Glycine	308E+06	318E+06	327E+06	778E+06	900E+06	884E+06	647E+06	461E+06	444E+06	728E+06	733E+06	716E+06	654E+06	605E+06	362E+05	344E+05
Alanine	233E+07	256E+07	191E+07	331E+07	446E+07	382E+07	193E+07	176E+07	138E+07	199E+07	222E+07	179E+07	241E+07	171E+07	117E+04	226E+03
Histidine	427E+06	487E+06	512E+06	314E+06	847E+06	519E+06	325E+06	295E+06	231E+06	505E+06	497E+06	491E+06	439E+06	429E+06	165E+06	100E+06
Proline	462E+07	491E+07	522E+07	508E+07	730E+07	575E+07	497E+07	368E+07	318E+07	764E+07	747E+07	797E+07	718E+07	668E+07	114E+07	114E+07
Serine	137E+07	135E+07	145E+07	114E+07	105E+07	125E+07	148E+07	124E+07	122E+07	172E+07	167E+07	147E+07	121E+07	111E+07	339E+06	343E+06
Tryptophan	816E+05	886E+05	934E+05	146E+06	133E+06	158E+06	156E+06	109E+06	126E+06	171E+06	152E+06	183E+06	136E+06	108E+06	957E+05	938E+05
Arginine	797E+06	799E+06	812E+06	549E+06	798E+06	538E+06	526E+06	562E+06	471E+06	679E+06	664E+06	533E+06	456E+06	549E+06	542E+06	548E+06
Asparagine	789E+07	806E+07	916E+07	103E+08	957E+07	847E+07	639E+07	499E+07	502E+07	743E+07	710E+07	781E+07	824E+07	694E+07	107E+07	111E+07
Threonine	310E+07	316E+07	319E+07	317E+07	459E+07	365E+07	256E+07	237E+07	209E+07	332E+07	325E+07	312E+07	286E+07	276E+07	428E+06	448E+06
Cysteine	608E+05	430E+05	733E+05	511E+05	908E+05	799E+05	286E+05	295E+05	161E+05	269E+05	217E+05	214E+05	302E+05	153E+05	141E+05	138E+05
Lysine	114E+06	105E+06	105E+06	765E+05	108E+06	774E+05	708E+05	770E+05	646E+05	943E+05	983E+05	742E+05	700E+05	753E+05	695E+05	824E+05
Aspartate	355E+07	351E+07	381E+07	840E+07	842E+07	709E+07	607E+07	611E+07	594E+07	418E+07	362E+07	357E+07	451E+07	377E+07	660E+06	642E+06
Tyrosine	598E+06	582E+06	720E+06	817E+06	921E+06	718E+06	495E+06	412E+06	395E+06	888E+06	732E+06	672E+06	574E+06	550E+06	213E+06	202E+06
Taurine	607E+05	551E+05	722E+05	134E+06	122E+06	488E+05	841E+05	387E+05	312E+05	779E+05	724E+05	906E+05	214E+06	160E+06	000E+00	279E+03
ADP	906E+06	725E+06	777E+06	705E+06	732E+06	594E+06	675E+06	367E+06	432E+06	496E+06	286E+06	306E+06	836E+06	718E+06	340E+05	325E+05
AMP	247E+06	216E+06	214E+06	213E+06	211E+06	137E+06	272E+06	131E+06	133E+06	215E+06	178E+06	186E+06	244E+06	252E+06	303E+05	256E+05
ATP	939E+07	790E+07	884E+07	136E+08	173E+08	145E+08	600E+07	418E+07	347E+07	663E+07	325E+07	350E+07	132E+08	651E+07	156E+05	128E+05
CDP	253E+05	193E+05	202E+05	310E+05	259E+05	284E+05	318E+05	133E+05	176E+05	283E+05	169E+05	171E+05	384E+05	313E+05	130E+04	185E+04
CMP	112E+05	108E+05	105E+05	138E+05	158E+05	154E+05	160E+05	134E+05	118E+05	270E+05	187E+05	263E+05	143E+05	162E+05	624E+03	102E+04
CTP	101E+06	878E+05	968E+05	143E+06	173E+06	178E+06	922E+05	703E+05	640E+05	132E+06	797E+05	821E+05	152E+06	955E+05	524E+04	404E+04
GDP	457E+05	443E+05	374E+05	538E+05	430E+05	365E+05	390E+05	187E+05	217E+05	456E+05	173E+05	234E+05	499E+05	379E+05	674E+04	542E+04
GMP	495E+05	503E+05	552E+05	904E+05	876E+05	213E+05	183E+05	189E+05	169E+05	896E+05	245E+05	251E+05	334E+05	266E+05	349E+04	134E+04
GTP	118E+06	108E+06	124E+06	171E+06	233E+06	200E+06	656E+05	433E+05	413E+05	104E+06	512E+05	451E+05	215E+06	906E+05	233E+04	313E+04
TDP	182E+05	125E+05	186E+05	188E+05	203E+05	181E+05	136E+05	515E+04	891E+04	160E+04	897E+03	234E+04	147E+05	123E+05	000E+00	384E+03
TMP	231E+04	108E+04	281E+04	330E+04	369E+04	385E+04	292E+04	228E+04	290E+04	445E+04	145E+04	174E+04	397E+04	381E+04	103E+04	566E+03
TTP	168E+05	113E+05	152E+05	359E+05	471E+05	527E+05	193E+05	174E+05	155E+05	228E+05	109E+05	132E+05	638E+05	387E+05	000E+00	184E+04
UDP	105E+06	790E+05	889E+05	132E+06	114E+06	128E+06	139E+06	675E+05	829E+05	104E+06	551E+05	601E+05	157E+06	142E+06	430E+04	260E+04
UMP	506E+05	408E+05	526E+05	433E+05	468E+05	384E+05	481E+05	424E+05	332E+05	200E+06	713E+05	675E+05	524E+05	468E+05	164E+04	116E+04
UTP	583E+06	446E+06	532E+06	130E+07	181E+07	216E+07	757E+06	527E+06	427E+06	885E+06	463E+06	467E+06	179E+07	869E+06	402E+04	289E+04
Methionine_sulfoxide	565E+05	659E+05	662E+05	656E+05	948E+05	744E+05	446E+05	514E+05	407E+05	875E+05	912E+05	861E+05	732E+05	757E+05	163E+05	174E+05
Cysteineglutathione_disulfide	812E+05	112E+06	167E+06	860E+05	120E+06	287E+05	298E+05	192E+05	803E+05	107E+06	564E+05	554E+05	433E+05	126E+06	136E+05	150E+05
Glutathione	329E+08	306E+08	304E+08	373E+08	407E+08	403E+08	244E+08	252E+08	245E+08	210E+08	206E+08	231E+08	349E+08	303E+08	536E+05	416E+05
NAD	171E+07	151E+07	175E+07	159E+07	186E+07	223E+07	122E+07	120E+07	130E+07	805E+06	754E+06	831E+06	173E+07	151E+07	000E+00	120E+04
Oxidized_glutathione	395E+05	666E+05	884E+05	819E+05	124E+06	439E+05	350E+05	268E+05	930E+05	131E+06	484E+05	399E+05	657E+05	249E+06	637E+03	148E+04
GDP-Mannose	983E+04	167E+05	426E+05	323E+04	118E+05	619E+04	000E+00	000E+00	251E+05	000E+00	985E+03	301E+05	923E+03	514E+05	000E+00	000E+00
GDP-Fucose	782E+05	809E+05	716E+05	933E+05	117E+06	110E+06	508E+05	473E+05	490E+05	622E+05	549E+05	541E+05	866E+05	620E+05	000E+00	728E+03
UDP-Hexose	268E+07	135E+07	195E+07	205E+07	172E+07	228E+07	188E+07	126E+07	103E+07	233E+07	213E+07	211E+07	289E+07	235E+07	688E+03	000E+00
UDP-glucuronic_acid	246E+06	203E+06	215E+06	730E+06	739E+06	850E+06	424E+06	275E+06	232E+06	795E+06	522E+06	504E+06	651E+06	435E+06	000E+00	000E+00
UDP-HexNac	241E+06	240E+06	113E+07	392E+06	625E+06	631E+06	282E+06	163E+06	228E+07	149E+06	142E+06	342E+07	365E+06	292E+07	875E+03	155E+04
Erythrose-P	831E+04	998E+04	112E+05	224E+05	248E+05	249E+05	199E+05	159E+05	948E+04	340E+05	133E+05	677E+04	215E+05	881E+04	425E+04	410E+04
Glycerol-P	123E+07	623E+06	671E+06	138E+07	478E+06	144E+07	123E+07	636E+06	526E+06	241E+07	212E+07	239E+07	856E+06	758E+06	281E+04	143E+04
Acetyl-CoA	380E+05	391E+05	381E+05	602E+05	892E+05	549E+05	355E+05	331E+05	287E+05	489E+05	430E+05	363E+05	814E+05	592E+05	000E+00	000E+00
Coenzyme_A	350E+05	324E+05	265E+05	186E+05	275E+05	245E+05	142E+05	114E+05	111E+05	149E+05	885E+04	659E+04	220E+05	105E+05	000E+00	510E+03
Creatine	410E+06	746E+06	703E+06	277E+06	434E+06	181E+06	750E+05	161E+06	165E+06	171E+06	177E+06	199E+06	438E+05	486E+05	000E+00	000E+00
4-Hydroxyproline	363E+07	392E+07	402E+07	426E+07	546E+07	398E+07	311E+07	264E+07	252E+07	362E+07	364E+07	379E+07	393E+07	351E+07	617E+06	703E+06
Betaine	127E+07	143E+07	152E+07	135E+07	174E+07	115E+07	117E+07	109E+07	923E+06	194E+07	189E+07	174E+07	131E+07	149E+07	774E+06	845E+06
CMP-sialic acid	710E+05	725E+05	871E+05	959E+05	130E+06	947E+05	586E+05	459E+05	623E+05	943E+05	804E+05	956E+05	840E+05	803E+05	000E+00	513E+03
Cyclic AMP	558E+05	475E+05	906E+05	623E+05	845E+05	706E+05	615E+05	532E+05	929E+05	130E+06	483E+05	748E+04	379E+05	115E+05	376E+04	110E+04
Cytidine	630E+04	177E+05	155E+05	296E+05	479E+05	122E+05	763E+04	154E+05	672E+04	346E+05	299E+05	114E+05	112E+05	250E+04	144E+05	000E+00
Glucuronate	416E+05	364E+05	294E+05	216E+05	239E+05	307E+05	292E+05	247E+05	210E+05	251E+05	208E+05	210E+05	287E+05	265E+05	225E+05	185E+05
FAD	101E+05	150E+05	165E+05	720E+04	139E+05	109E+05	511E+04	469E+04	803E+04	103E+05	589E+04	379E+04	832E+04	566E+04	000E+00	000E+00
Guanosine	788E+04	664E+04	827E+04	523E+04	947E+04	138E+05	131E+05	110E+05	178E+05	137E+05	154E+05	159E+05	778E+04	106E+05	115E+05	102E+05
Hypoxanthine	303E+05	357E+05	482E+05	241E+05	118E+06	510E+05	104E+05	158E+05	121E+05	333E+05	338E+05	280E+05	158E+05	173E+05	000E+00	496E+03
Inosine	988E+04	925E+04	722E+04	810E+04	197E+05	237E+05	177E+05	219E+05	201E+05	382E+05	409E+05	332E+05	101E+05	135E+05	450E+04	172E+04
L-Citrulline	123E+04	104E+04	364E+04	194E+04	168E+03	252E+04	165E+04	173E+04	467E+04	218E+04	829E+03	105E+04	329E+03	333E+04	560E+03	135E+04
N-Acetyl-aspartate	668E+08	569E+08	636E+08	738E+08	875E+08	988E+08	589E+08	664E+08	673E+08	412E+08	401E+08	403E+08	589E+08	529E+08	451E+05	471E+05
N-Acetylneuraminic_acid	656E+05	521E+05	659E+05	110E+06	171E+06	141E+06	179E+06	126E+06	128E+06	230E+06	160E+06	204E+06	209E+06	208E+06	281E+05	227E+05
Orotic acid	334E+04	157E+04	276E+04	186E+04	273E+04	129E+04	175E+04	530E+04	988E+04	199E+04	141E+04	340E+04	232E+04	233E+04	904E+03	132E+04
Riboflavin	317E+04	405E+04	537E+04	379E+04	556E+04	420E+04	410E+04	414E+04	217E+04	392E+04	258E+04	373E+04	162E+04	273E+04	341E+04	395E+04
Polyol-P	123E+05	619E+04	562E+04	848E+04	143E+04	107E+05	487E+04	312E+04	370E+04	148E+05	175E+05	154E+05	498E+04	556E+04	172E+04	127E+04
Thymidine	199E+07	653E+06	185E+05	287E+07	173E+07	468E+07	299E+07	323E+07	155E+05	109E+07	957E+06	130E+05	267E+07	170E+05	304E+07	685E+04
Thymine	926E+05	837E+05	102E+06	894E+05	726E+05	607E+05	461E+05	462E+05	448E+05	330E+05	410E+05	255E+05	499E+05	500E+05	106E+05	131E+05
Uracil	766E+05	742E+05	856E+05	833E+05	807E+05	617E+05	548E+05	433E+05	539E+05	625E+05	670E+05	703E+05	662E+05	577E+05	762E+04	181E+05
Uridine	545E+05	577E+05	935E+05	698E+05	228E+06	857E+05	307E+05	540E+05	352E+05	725E+05	750E+05	668E+05	440E+05	537E+05	553E+04	567E+04
Xanthine	748E+05	689E+05	752E+05	213E+05	184E+06	121E+06	634E+05	501E+05	450E+05	691E+05	868E+05	832E+05	768E+05	846E+05	189E+05	196E+05
XMP	453E+04	238E+04	629E+04	308E+04	184E+04	484E+04	166E+04	345E+04	395E+04	376E+03	375E+03	240E+04	376E+04	446E+04	355E+03	743E+03
Ribose-P	155008919	6955539	222200181	98326819	152649364	110642445	177803603	218740029	173870214	239769664	221267964	193778114	14632646	156479584	12686264	28060204
Sedoheptulose	5090783	3470142	11065391	12263161	11978576	9139336	8211402	16936732	16301612	72952	5480921	6115328	788094	10642308	5730974	223427
Sedoheptulose-P	103179985	50553596	72448298	100148208	56319366	99166304	110390104	81246311	88653295	97892146	76041302	109991244	11488913	1047234	1152746	1285067
Propionyl-CoA	41576323	31761612	15431473	50607368	52928307	47801606	32738352	28176887	11651777	39797752	24683426	8820302	56958365	12090407	0	51458
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	HMDB
PEP	HMDB0000263
Lactate	HMDB0000190
Hexose-P	HMDB000140
Hexose	HMDB0000122
Glyceraldehyde-phosphate	HMDB0001112
DHAP	HMDB0001473
Hexose-bisphosphate	HMDB0001058
Hexosamine-phosphate	HMDB0001254
Pyruvate	HMDB0000243
Pentitol	HMDB0000508
Polyol	HMDB0000247
Fumarate	HMDB0000134
(Iso)citrate	HMDB0000094
Malate	HMDB0000156
Oxoglutarate	HMDB0000208
Succinate	HMDB0000254
Aconitate	HMDB0000072
Glutamate	HMDB0000148
Glutamine	HMDB0000641
Methionine	HMDB0000696
Phenylalanine	HMDB0000159
Glycine	HMDB0000123
Alanine	HMDB0000161
Histidine	HMDB0000177
Proline	HMDB0000162
Serine	HMDB0000187
Tryptophan	HMDB0000929
Arginine	HMDB0000517
Asparagine	HMDB0000168
Threonine	HMDB0000167
Cysteine	HMDB0000574
Lysine	HMDB0000182
Aspartate	HMDB0000191
Tyrosine	HMDB0000158
Taurine	HMDB0000251
ADP	HMDB0001341
AMP	HMDB0000045
ATP	HMDB0000538
CDP	HMDB0001546
CMP	HMDB0000095
CTP	HMDB0000082
GDP	HMDB0001201
GMP	HMDB0001397
GTP	HMDB0001273
TDP	HMDB0001274
TMP	HMDB0002666
TTP	HMDB0001342
UDP	HMDB0000295
UMP	HMDB0000288
UTP	HMDB0000285
Methionine_sulfoxide	HMDB0002005
Cysteineglutathione_disulfide	HMDB0000656
Glutathione	HMDB0000125
NAD	HMDB0000902
Oxidized_glutathione	HMDB0003337
GDP-Mannose	HMDB0001163
GDP-Fucose	HMDB0001095
UDP-Hexose	HMDB0000286
UDP-glucuronic_acid	HMDB0000935
UDP-HexNac	HMDB0000290
Erythrose-P	HMDB0001321
Glycerol-P	HMDB0000126
Acetyl-CoA	HMDB0001206
Coenzyme_A	HMDB0001423
Creatine	HMDB0000064
4-Hydroxyproline	HMDB0000725
Betaine	HMDB0000725
CMP-sialic acid	HMDB0001176
Cyclic AMP	HMDB0000058
Cytidine	HMDB0000089
Glucuronate	HMDB0000127
FAD	HMDB0001248
Guanosine	HMDB0000133
Hypoxanthine	HMDB0000157
Inosine	HMDB0000195
L-Citrulline	HMDB0000904
N-Acetyl-aspartate	HMDB0000812
N-Acetylneuraminic_acid	HMDB0000230
Orotic acid	HMDB0000226
Riboflavin	HMDB0000244
Polyol-P	HMDB0062530
Thymidine	HMDB0000273
Thymine	HMDB0000262
Uracil	HMDB0000300
Uridine	HMDB0000296
Xanthine	HMDB0000292
XMP	HMDB0001554
Ribose-P	HMDB0001548
Sedoheptulose	HMDB0003219
Sedoheptulose-P	HMDB0001068
Propionyl-CoA	HMDB0001275
METABOLITES_END
#END