#METABOLOMICS WORKBENCH javier_frontinan_20220425_002153 DATATRACK_ID:3217 STUDY_ID:ST002157 ANALYSIS_ID:AN003532 PROJECT_ID:PR001370
VERSION             	1
CREATED_ON             	April 30, 2022, 7:29 am
#PROJECT
PR:PROJECT_TITLE                 	Effect of long-term exposure to graphene on skin cell metabolism
PR:PROJECT_TYPE                  	MS HaCaT Cells
PR:PROJECT_SUMMARY               	Graphene-derived materials are a family of nanomaterials with multiple potential
PR:PROJECT_SUMMARY               	applications in different fields such as biomedicine. It is therefore essential
PR:PROJECT_SUMMARY               	to understand their interaction with cellular barriers such as skin. In this
PR:PROJECT_SUMMARY               	work we evaluated the metabolic changes in human skin cells (HaCaT) exposed to
PR:PROJECT_SUMMARY               	different GRMs for 7 and 30 days. Objectives Endogenous metabolic profiles of
PR:PROJECT_SUMMARY               	control and graphene-treated keratinocytes have been studied using ultra-high
PR:PROJECT_SUMMARY               	performance liquid chromatography – mass spectrometry (UHPLC-MS).
PR:PROJECT_SUMMARY               	Keratinocytes were treated with graphene oxide (GO) from two different suppliers
PR:PROJECT_SUMMARY               	and with few layer graphene (FLG). Samples were collected one week and one month
PR:PROJECT_SUMMARY               	after the start of the treatment. The general aim of the project was to evaluate
PR:PROJECT_SUMMARY               	potential metabolic differences between: 1) Graphene-treated keratinocytes and
PR:PROJECT_SUMMARY               	control keratinocytes at one week; 2) Graphene-treated keratinocytes and control
PR:PROJECT_SUMMARY               	keratinocytes at one month; 3) Control keratinocytes at 1 month and 1 week; 4)
PR:PROJECT_SUMMARY               	Graphene-treated keratinocytes at 1 month and 1 week. Experimental Procedures A
PR:PROJECT_SUMMARY               	successful metabolic profiling experiment relies on the ability to determine
PR:PROJECT_SUMMARY               	changes in an organism’s biofluid or tissue complement of metabolites. Mass
PR:PROJECT_SUMMARY               	spectrometry coupled to ultra-high performance liquid chromatography (UHPLC-MS)
PR:PROJECT_SUMMARY               	is well suited to such analyses due to its high sensitivity, large coverage over
PR:PROJECT_SUMMARY               	different classes of metabolites, high throughput capacity, and wide dynamic
PR:PROJECT_SUMMARY               	range. In this study, one UHPLC-MS based platform was used to analyse endogenous
PR:PROJECT_SUMMARY               	analytes for inclusion in subsequent statistical analysis procedures used to
PR:PROJECT_SUMMARY               	study metabolic differences between the groups of samples.
PR:INSTITUTE                     	University of Castilla-La Mancha
PR:DEPARTMENT                    	Medical Sciences
PR:LABORATORY                    	Group of Oxidative Stress and Neurodegeneration
PR:LAST_NAME                     	Frontiñán
PR:FIRST_NAME                    	Javier
PR:ADDRESS                       	F. Medicina Camino de Moledores s/n 13071
PR:EMAIL                         	javier.frontinan@uclm.es
PR:PHONE                         	+34656967979
PR:FUNDING_SOURCE                	Graphene Flagship (EU)
#STUDY
ST:STUDY_TITLE                   	Effect of long-term exposure to graphene on skin cell metabolism
ST:STUDY_SUMMARY                 	Graphene-derived materials are a family of nanomaterials with multiple potential
ST:STUDY_SUMMARY                 	applications in different fields such as biomedicine. It is therefore essential
ST:STUDY_SUMMARY                 	to understand their interaction with cellular barriers such as skin. In this
ST:STUDY_SUMMARY                 	work we evaluated the metabolic changes in human skin cells (HaCaT) exposed to
ST:STUDY_SUMMARY                 	different GRMs for 7 and 30 days. Objectives Endogenous metabolic profiles of
ST:STUDY_SUMMARY                 	control and graphene-treated keratinocytes have been studied using ultra-high
ST:STUDY_SUMMARY                 	performance liquid chromatography – mass spectrometry (UHPLC-MS).
ST:STUDY_SUMMARY                 	Keratinocytes were treated with graphene oxide (GO) from two different suppliers
ST:STUDY_SUMMARY                 	and with few layer graphene (FLG). Samples were collected one week and one month
ST:STUDY_SUMMARY                 	after the start of the treatment. The general aim of the project was to evaluate
ST:STUDY_SUMMARY                 	potential metabolic differences between: 1) Graphene-treated keratinocytes and
ST:STUDY_SUMMARY                 	control keratinocytes at one week; 2) Graphene-treated keratinocytes and control
ST:STUDY_SUMMARY                 	keratinocytes at one month; 3) Control keratinocytes at 1 month and 1 week; 4)
ST:STUDY_SUMMARY                 	Graphene-treated keratinocytes at 1 month and 1 week. Experimental Procedures A
ST:STUDY_SUMMARY                 	successful metabolic profiling experiment relies on the ability to determine
ST:STUDY_SUMMARY                 	changes in an organism’s biofluid or tissue complement of metabolites. Mass
ST:STUDY_SUMMARY                 	spectrometry coupled to ultra-high performance liquid chromatography (UHPLC-MS)
ST:STUDY_SUMMARY                 	is well suited to such analyses due to its high sensitivity, large coverage over
ST:STUDY_SUMMARY                 	different classes of metabolites, high throughput capacity, and wide dynamic
ST:STUDY_SUMMARY                 	range. In this study, one UHPLC-MS based platform was used to analyse endogenous
ST:STUDY_SUMMARY                 	analytes for inclusion in subsequent statistical analysis procedures used to
ST:STUDY_SUMMARY                 	study metabolic differences between the groups of samples. Results The oxidation
ST:STUDY_SUMMARY                 	degree and size of the GRMs is determinant in the effect on cell metabolism, as
ST:STUDY_SUMMARY                 	well as the exposure time. Thus, one of the materials used generated a change in
ST:STUDY_SUMMARY                 	the energy metabolism of the cells, significantly increasing the level of
ST:STUDY_SUMMARY                 	different Krebs cycle metabolites.
ST:INSTITUTE                     	University of Castilla-La Mancha
ST:DEPARTMENT                    	Medical Sciences
ST:LABORATORY                    	Group of Oxidative Stress and Neurodegeneration
ST:LAST_NAME                     	Frontinan
ST:FIRST_NAME                    	Javier
ST:ADDRESS                       	F. Medicina Camino de Moledores s/n 13071
ST:EMAIL                         	javier.frontinan@uclm.es
ST:PHONE                         	+34656967979
ST:NUM_GROUPS                    	8
#SUBJECT
SU:SUBJECT_TYPE                  	Cultured cells
SU:SUBJECT_SPECIES               	Homo sapiens
SU:TAXONOMY_ID                   	9606
SU:GENDER                        	Male
SU:CELL_BIOSOURCE_OR_SUPPLIER    	CLS
SU:CELL_STRAIN_DETAILS           	In vitro spontaneously transformed keratinocytes from histologically normal skin
SU:CELL_PRIMARY_IMMORTALIZED     	HaCaT
SU:CELL_PASSAGE_NUMBER           	Up to the 15th passage
#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           	-	190905_19_0009_UCLM_CCM_001	Exposure time:- | Nanomaterial:- | Replicate:-	COD.OWL=REF_CCM_04; COD.EXT=-; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_001.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_002	Exposure time:- | Nanomaterial:- | Replicate:-	COD.OWL=REF_CCM_04; COD.EXT=-; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_002.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_003	Exposure time:- | Nanomaterial:- | Replicate:-	COD.OWL=OWL-MIX-074; COD.EXT=-; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_003.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_004	Exposure time:- | Nanomaterial:- | Replicate:-	COD.OWL=OWL-MIX-074; COD.EXT=-; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_004.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_005	Exposure time:- | Nanomaterial:- | Replicate:-	COD.OWL=AA_CCM; COD.EXT=-; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_005.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_006	Exposure time:- | Nanomaterial:- | Replicate:-	COD.OWL=AA_CCM; COD.EXT=-; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_006.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_007	Exposure time:- | Nanomaterial:- | Replicate:-	COD.OWL=Equilibration; COD.EXT=-; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_007.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_008	Exposure time:- | Nanomaterial:- | Replicate:-	COD.OWL=Equilibration; COD.EXT=-; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_008.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_009	Exposure time:- | Nanomaterial:- | Replicate:-	COD.OWL=BLK; COD.EXT=-; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_009.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_010	Exposure time:- | Nanomaterial:- | Replicate:-	COD.OWL=Equilibration; COD.EXT=-; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_010.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_011	Exposure time:- | Nanomaterial:- | Replicate:-	COD.OWL=Pool 01; COD.EXT=-; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_011.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_012	Exposure time:Week | Nanomaterial:GO | Replicate:N1	COD.OWL=Owl-1909-011; COD.EXT=1w GO N1; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_012.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_013	Exposure time:Month | Nanomaterial:FLG | Replicate:N4	COD.OWL=Owl-1909-074; COD.EXT=1m FLG N4; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_013.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_014	Exposure time:Week | Nanomaterial:FLG | Replicate:N1	COD.OWL=Owl-1909-031; COD.EXT=1w FLG N1; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_014.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_015	Exposure time:Week | Nanomaterial:GO | Replicate:N3	COD.OWL=Owl-1909-013; COD.EXT=1w GO N3; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_015.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_016	Exposure time:- | Nanomaterial:- | Replicate:-	COD.OWL=SeraM-04 01; COD.EXT=-; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_016.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_017	Exposure time:- | Nanomaterial:- | Replicate:-	COD.OWL=Pool 02; COD.EXT=-; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_017.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_018	Exposure time:Month | Nanomaterial:GO- | Replicate:N1	COD.OWL=Owl-1909-056; COD.EXT=1m GO- N1; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_018.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_019	Exposure time:Month | Nanomaterial:GO | Replicate:N5	COD.OWL=Owl-1909-055; COD.EXT=1m GO N5; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_019.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_020	Exposure time:Week | Nanomaterial:C | Replicate:N1	COD.OWL=Owl-1909-001; COD.EXT=1w C N1; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_020.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_021	Exposure time:Week | Nanomaterial:GO g- | Replicate:N1	COD.OWL=Owl-1909-026; COD.EXT=1w GOg- N1; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_021.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_022	Exposure time:Month | Nanomaterial:GO g | Replicate:N4	COD.OWL=Owl-1909-064; COD.EXT=1m GOg N4; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_022.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_023	Exposure time:Week | Nanomaterial:GO g | Replicate:N1	COD.OWL=Owl-1909-021; COD.EXT=1w GOg N1; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_023.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_024	Exposure time:Month | Nanomaterial:FLG | Replicate:N1	COD.OWL=Owl-1909-071; COD.EXT=1m FLG N1; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_024.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_025	Exposure time:Week | Nanomaterial:C | Replicate:N4	COD.OWL=Owl-1909-004; COD.EXT=1w C N4; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_025.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_026	Exposure time:- | Nanomaterial:- | Replicate:-	COD.OWL=SeraM-04 02; COD.EXT=-; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_026.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_027	Exposure time:- | Nanomaterial:- | Replicate:-	COD.OWL=Pool 03; COD.EXT=-; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_027.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_028	Exposure time:Month | Nanomaterial:GO g | Replicate:N2	COD.OWL=Owl-1909-062; COD.EXT=1m GOg N2; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_028.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_029	Exposure time:Month | Nanomaterial:GO | Replicate:N2	COD.OWL=Owl-1909-052; COD.EXT=1m GO N2; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_029.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_030	Exposure time:Month | Nanomaterial:C | Replicate:N4	COD.OWL=Owl-1909-044; COD.EXT=1m C N4; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_030.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_031	Exposure time:Month | Nanomaterial:GO g- | Replicate:N1	COD.OWL=Owl-1909-066; COD.EXT=1m GOg- N1; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_031.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_032	Exposure time:Week | Nanomaterial:FLG- | Replicate:N1	COD.OWL=Owl-1909-036; COD.EXT=1w FLG- N1; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_032.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_033	Exposure time:Week | Nanomaterial:GO g | Replicate:N5	COD.OWL=Owl-1909-025; COD.EXT=1w GOg N5; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_033.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_034	Exposure time:Week | Nanomaterial:GO g | Replicate:N4	COD.OWL=Owl-1909-024; COD.EXT=1w GOg N4; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_034.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_035	Exposure time:Month | Nanomaterial:GO g | Replicate:N5	COD.OWL=Owl-1909-065; COD.EXT=1m GOg N5; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_035.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_036	Exposure time:- | Nanomaterial:- | Replicate:-	COD.OWL=SeraM-04 03; COD.EXT=-; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_036.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_037	Exposure time:- | Nanomaterial:- | Replicate:-	COD.OWL=Pool 04; COD.EXT=-; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_037.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_038	Exposure time:Month | Nanomaterial:FLG | Replicate:N5	COD.OWL=Owl-1909-075; COD.EXT=1m FLG N5; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_038.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_039	Exposure time:Week | Nanomaterial:C | Replicate:N5	COD.OWL=Owl-1909-005; COD.EXT=1w C N5; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_039.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_040	Exposure time:Week | Nanomaterial:GO | Replicate:N4	COD.OWL=Owl-1909-014; COD.EXT=1w GO N4; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_040.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_041	Exposure time:Month | Nanomaterial:GO | Replicate:N1	COD.OWL=Owl-1909-051; COD.EXT=1m GO N1; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_041.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_042	Exposure time:Month | Nanomaterial:GO g | Replicate:N1	COD.OWL=Owl-1909-061; COD.EXT=1m GOg N1; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_042.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_043	Exposure time:Month | Nanomaterial:C- | Replicate:N1	COD.OWL=Owl-1909-046; COD.EXT=1m C- N1; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_043.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_044	Exposure time:Week | Nanomaterial:FLG | Replicate:N3	COD.OWL=Owl-1909-033; COD.EXT=1w FLG N3; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_044.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_045	Exposure time:Week | Nanomaterial:GO- | Replicate:N1	COD.OWL=Owl-1909-016; COD.EXT=1w GO- N1; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_045.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_046	Exposure time:- | Nanomaterial:- | Replicate:-	COD.OWL=SeraM-04 04; COD.EXT=-; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_046.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_047	Exposure time:- | Nanomaterial:- | Replicate:-	COD.OWL=Pool 05; COD.EXT=-; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_047.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_048	Exposure time:Week | Nanomaterial:C- | Replicate:N1	COD.OWL=Owl-1909-006; COD.EXT=1w C- N1; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_048.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_049	Exposure time:Month | Nanomaterial:C | Replicate:N2	COD.OWL=Owl-1909-042; COD.EXT=1m C N2; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_049.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_050	Exposure time:Month | Nanomaterial:C | Replicate:N3	COD.OWL=Owl-1909-043; COD.EXT=1m C N3; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_050.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_051	Exposure time:Week | Nanomaterial:FLG | Replicate:N5	COD.OWL=Owl-1909-035; COD.EXT=1w FLG N5; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_051.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_052	Exposure time:Month | Nanomaterial:FLG | Replicate:N3	COD.OWL=Owl-1909-073; COD.EXT=1m FLG N3; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_052.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_053	Exposure time:Month | Nanomaterial:FLG | Replicate:N2	COD.OWL=Owl-1909-072; COD.EXT=1m FLG N2; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_053.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_054	Exposure time:Week | Nanomaterial:FLG | Replicate:N2	COD.OWL=Owl-1909-032; COD.EXT=1w FLG N2; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_054.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_055	Exposure time:Month | Nanomaterial:GO | Replicate:N4	COD.OWL=Owl-1909-054; COD.EXT=1m GO N4; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_055.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_056	Exposure time:- | Nanomaterial:- | Replicate:-	COD.OWL=SeraM-04 05; COD.EXT=-; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_056.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_057	Exposure time:- | Nanomaterial:- | Replicate:-	COD.OWL=Pool 06; COD.EXT=-; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_057.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_058	Exposure time:Week | Nanomaterial:FLG | Replicate:N4	COD.OWL=Owl-1909-034; COD.EXT=1w FLG N4; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_058.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_059	Exposure time:Month | Nanomaterial:C | Replicate:N1	COD.OWL=Owl-1909-041; COD.EXT=1m C N1; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_059.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_060	Exposure time:Month | Nanomaterial:C | Replicate:N5	COD.OWL=Owl-1909-045; COD.EXT=1m C N5; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_060.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_061	Exposure time:Week | Nanomaterial:C | Replicate:N3	COD.OWL=Owl-1909-003; COD.EXT=1w C N3; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_061.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_062	Exposure time:Month | Nanomaterial:FLG- | Replicate:N1	COD.OWL=Owl-1909-076; COD.EXT=1m FLG- N1; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_062.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_063	Exposure time:Week | Nanomaterial:GO | Replicate:N5	COD.OWL=Owl-1909-015; COD.EXT=1w GO N5; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_063.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_064	Exposure time:Month | Nanomaterial:GO g | Replicate:N3	COD.OWL=Owl-1909-063; COD.EXT=1m GOg N3; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_064.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_065	Exposure time:Week | Nanomaterial:GO g | Replicate:N2	COD.OWL=Owl-1909-022; COD.EXT=1w GOg N2; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_065.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_066	Exposure time:- | Nanomaterial:- | Replicate:-	COD.OWL=SeraM-04 06; COD.EXT=-; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_066.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_067	Exposure time:- | Nanomaterial:- | Replicate:-	COD.OWL=Pool 07; COD.EXT=-; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_067.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_068	Exposure time:Week | Nanomaterial:GO g | Replicate:N3	COD.OWL=Owl-1909-023; COD.EXT=1w GOg N3; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_068.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_069	Exposure time:Month | Nanomaterial:GO | Replicate:N3	COD.OWL=Owl-1909-053; COD.EXT=1m GO N3; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_069.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_070	Exposure time:Week | Nanomaterial:C | Replicate:N2	COD.OWL=Owl-1909-002; COD.EXT=1w C N2; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_070.raw
SUBJECT_SAMPLE_FACTORS           	-	190905_19_0009_UCLM_CCM_071	Exposure time:Week | Nanomaterial:GO | Replicate:N2	COD.OWL=Owl-1909-012; COD.EXT=1w GO N2; RAW_FILE_NAME=190905_19_0009_UCLM_CCM_071.raw
#COLLECTION
CO:COLLECTION_SUMMARY            	HaCaT cells treated with GO1, GO2 and FLG
CO:SAMPLE_TYPE                   	Keratinocytes
CO:STORAGE_CONDITIONS            	-80℃
#TREATMENT
TR:TREATMENT_SUMMARY             	Cells were treated with 5 ug/mL of the different GRMs for 7 days and 30 days (1
TR:TREATMENT_SUMMARY             	treatment/week)
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	Keratinocytes were defrosted on ice and proteins were precipitated from the
SP:SAMPLEPREP_SUMMARY            	lysed cell samples by adding the extraction solvent spiked with metabolites not
SP:SAMPLEPREP_SUMMARY            	detected in unspiked cell extracts. These metabolites, considered as internal
SP:SAMPLEPREP_SUMMARY            	standards, were tryptophan-d5, Anthranilic acid-(ring-13C6), Phenylthiohydantoin
SP:SAMPLEPREP_SUMMARY            	(PTH)-valine, Glycocholic-2,2,4,4-d4 acid (Sigma Aldrich). Then, cell extracts
SP:SAMPLEPREP_SUMMARY            	were incubated at -20 ˚C for 1 hour and after that, samples were vortexed and
SP:SAMPLEPREP_SUMMARY            	centrifuged at 18,000 x g for 10 minutes at 4 ºC. Supernatants were collected
SP:SAMPLEPREP_SUMMARY            	and kept on ice. A second extraction was performed from the remaining pellets,
SP:SAMPLEPREP_SUMMARY            	following the same steps described above. Supernatants obtained from the second
SP:SAMPLEPREP_SUMMARY            	extraction were collected and put together with the supernatants of the first
SP:SAMPLEPREP_SUMMARY            	extraction. Finally, these supernatants were dried under vacuum, reconstituted
SP:SAMPLEPREP_SUMMARY            	in water, resuspended with agitation for 10 minutes, centrifuged at 18,000 x g
SP:SAMPLEPREP_SUMMARY            	for 5 minutes at 4ºC, and transferred to vials for UHPLC-MS analysis.
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_SUMMARY        	Chromatography was performed on a 1.0-mm internal diameter x 150 mm Acquity HSS
CH:CHROMATOGRAPHY_SUMMARY        	T3 1.7 µm column (Waters Corp., Milford, MA) using an ACQUITY UPLC system
CH:CHROMATOGRAPHY_SUMMARY        	(Waters Corp.). The column was maintained at 40 ºC. Samples (2µL) were
CH:CHROMATOGRAPHY_SUMMARY        	injected onto the column at a flow rate of 100 µL/min, for a total run time of
CH:CHROMATOGRAPHY_SUMMARY        	25 min. The following linear elution gradient was used: 100% solvent A (10mM
CH:CHROMATOGRAPHY_SUMMARY        	tributylamine + 15mM acetic acid + 0.2% methanol in water), to which solvent B
CH:CHROMATOGRAPHY_SUMMARY        	(methanol) was added incrementally to reach a concentration of 4% B after 1.5
CH:CHROMATOGRAPHY_SUMMARY        	min, increasing to 20% B at 3 min, 25% B at 8 min, 50% B at 10 min, 55% at 15
CH:CHROMATOGRAPHY_SUMMARY        	min, and 100% B over the next 5 min, and returning to the initial composition
CH:CHROMATOGRAPHY_SUMMARY        	over the final 5 min.
CH:CHROMATOGRAPHY_TYPE           	Ion pairing
CH:INSTRUMENT_NAME               	Waters Acquity H-Class
CH:COLUMN_NAME                   	Waters Acquity BEH HSS T3 (100 x 2.1mm, 1.8um)
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:INSTRUMENT_NAME               	Waters LCT premier
MS:INSTRUMENT_TYPE               	Time of flight
MS:MS_TYPE                       	ESI
MS:ION_MODE                      	NEGATIVE
MS:MS_COMMENTS                   	The eluent was introduced into the mass spectrometer (LCT Premier (Waters Corp.)
MS:MS_COMMENTS                   	by electrospray ionization, with capillary and cone voltages set in the negative
MS:MS_COMMENTS                   	ion mode to 2800 and 100 V, respectively. The nebulization gas was set to 600
MS:MS_COMMENTS                   	L/hour and 300ºC. The cone gas was fixed at 50 L/hour, and the source
MS:MS_COMMENTS                   	temperature was maintained at 120ºC. Centroid data were acquired over the mass
MS:MS_COMMENTS                   	range of 50-1000 Da, using an accumulation time of 0.2 seconds per spectrum. All
MS:MS_COMMENTS                   	spectra were mass corrected in real time by reference to leucine enkephalin,
MS:MS_COMMENTS                   	infused at 10 µL/minute through an independent reference electrospray, sampled
MS:MS_COMMENTS                   	every 10 seconds.
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	Log2 (fold-change)
MS_METABOLITE_DATA_START
Samples	190905_19_0009_UCLM_CCM_020	190905_19_0009_UCLM_CCM_070	190905_19_0009_UCLM_CCM_061	190905_19_0009_UCLM_CCM_025	190905_19_0009_UCLM_CCM_039	190905_19_0009_UCLM_CCM_012	190905_19_0009_UCLM_CCM_071	190905_19_0009_UCLM_CCM_015	190905_19_0009_UCLM_CCM_040	190905_19_0009_UCLM_CCM_063	190905_19_0009_UCLM_CCM_023	190905_19_0009_UCLM_CCM_065	190905_19_0009_UCLM_CCM_068	190905_19_0009_UCLM_CCM_034	190905_19_0009_UCLM_CCM_033	190905_19_0009_UCLM_CCM_014	190905_19_0009_UCLM_CCM_054	190905_19_0009_UCLM_CCM_044	190905_19_0009_UCLM_CCM_058	190905_19_0009_UCLM_CCM_051	190905_19_0009_UCLM_CCM_059	190905_19_0009_UCLM_CCM_049	190905_19_0009_UCLM_CCM_050	190905_19_0009_UCLM_CCM_030	190905_19_0009_UCLM_CCM_060	190905_19_0009_UCLM_CCM_041	190905_19_0009_UCLM_CCM_029	190905_19_0009_UCLM_CCM_069	190905_19_0009_UCLM_CCM_055	190905_19_0009_UCLM_CCM_019	190905_19_0009_UCLM_CCM_042	190905_19_0009_UCLM_CCM_028	190905_19_0009_UCLM_CCM_064	190905_19_0009_UCLM_CCM_022	190905_19_0009_UCLM_CCM_035	190905_19_0009_UCLM_CCM_024	190905_19_0009_UCLM_CCM_053	190905_19_0009_UCLM_CCM_052	190905_19_0009_UCLM_CCM_013	190905_19_0009_UCLM_CCM_038
Factors	Exposure time:Week | Nanomaterial:C | Replicate:N1	Exposure time:Week | Nanomaterial:C | Replicate:N2	Exposure time:Week | Nanomaterial:C | Replicate:N3	Exposure time:Week | Nanomaterial:C | Replicate:N4	Exposure time:Week | Nanomaterial:C | Replicate:N5	Exposure time:Week | Nanomaterial:GO | Replicate:N1	Exposure time:Week | Nanomaterial:GO | Replicate:N2	Exposure time:Week | Nanomaterial:GO | Replicate:N3	Exposure time:Week | Nanomaterial:GO | Replicate:N4	Exposure time:Week | Nanomaterial:GO | Replicate:N5	Exposure time:Week | Nanomaterial:GO g | Replicate:N1	Exposure time:Week | Nanomaterial:GO g | Replicate:N2	Exposure time:Week | Nanomaterial:GO g | Replicate:N3	Exposure time:Week | Nanomaterial:GO g | Replicate:N4	Exposure time:Week | Nanomaterial:GO g | Replicate:N5	Exposure time:Week | Nanomaterial:FLG | Replicate:N1	Exposure time:Week | Nanomaterial:FLG | Replicate:N2	Exposure time:Week | Nanomaterial:FLG | Replicate:N3	Exposure time:Week | Nanomaterial:FLG | Replicate:N4	Exposure time:Week | Nanomaterial:FLG | Replicate:N5	Exposure time:Month | Nanomaterial:C | Replicate:N1	Exposure time:Month | Nanomaterial:C | Replicate:N2	Exposure time:Month | Nanomaterial:C | Replicate:N3	Exposure time:Month | Nanomaterial:C | Replicate:N4	Exposure time:Month | Nanomaterial:C | Replicate:N5	Exposure time:Month | Nanomaterial:GO | Replicate:N1	Exposure time:Month | Nanomaterial:GO | Replicate:N2	Exposure time:Month | Nanomaterial:GO | Replicate:N3	Exposure time:Month | Nanomaterial:GO | Replicate:N4	Exposure time:Month | Nanomaterial:GO | Replicate:N5	Exposure time:Month | Nanomaterial:GO g | Replicate:N1	Exposure time:Month | Nanomaterial:GO g | Replicate:N2	Exposure time:Month | Nanomaterial:GO g | Replicate:N3	Exposure time:Month | Nanomaterial:GO g | Replicate:N4	Exposure time:Month | Nanomaterial:GO g | Replicate:N5	Exposure time:Month | Nanomaterial:FLG | Replicate:N1	Exposure time:Month | Nanomaterial:FLG | Replicate:N2	Exposure time:Month | Nanomaterial:FLG | Replicate:N3	Exposure time:Month | Nanomaterial:FLG | Replicate:N4	Exposure time:Month | Nanomaterial:FLG | Replicate:N5
L-Leucine	082111098	0614364186	1446385234	0946129261	0769052461	0993390967	0929253355	1995960482	1084588225	1218493312	0873790217	08644051	1840345892	1028031702	1254007268	0850680623	1045381649	1155284935	0895702002	0857649294	0701389996	0818321511	079023769	0782607899	1075983463	1095778744	1043061865	1511902787	1447082492	0729706285	1019135897	1119829651	1461501974	1423954291	1027516362	1445444835	063085022	0910337698	1111787439	0386381245
L-Asparagine	1432776353	0783619934	1591048853	0783005084	1013159221	1846232172	1075082241	3207784517	1107186744	129344355	0897545177	1024084015	2554949202	1293053198	1536527701	1124484431	097474866	1134320522	1086016146	1111004373	1130294354	0988015255	0765511305	0845618659	2455916099	0703408065	138165536	1637888663	1186130707	089309092	109887936	109731979	1565926842	1691575472	1300755591	1272540696	0801789635	0858022837	0989108624	063222618
L-Aspartic acid	0394285389	0183256644	075159538	0487008012	0442953724	0545938861	0556373139	0696420934	0861015719	0631061965	0540073496	0393296104	0739110914	0713262151	042686766	0724681279	0682085237	0517687254	0616306354	0401322488	0204405834	0359298236	113328319	1082251667	1671660038	0504185524	0675205427	2542572902	23181921	1220704585	0776290951	0871565794	263890983	1816527078	284226466	0985719047	0257480668	2324584002	2306155083	0588908774
L-Glutamine	1161209854	0860093175	0470994076	1225086597	0721396275	1422491216	1328854951	0605247385	0787939473	0937912977	0630894966	1246665895	0403808539	0636615536	0351262918	0903176947	1421890769	0335412019	0847863515	1025292695	0946581891	081097993	0926229295	0882688693	165987103	1091269684	0867644982	100995308	1497643443	1946966987	0941373426	0858594618	1157720079	1125934618	1684047161	107807843	075824549	1109206332	1650912507	1291716286
L-Lysine	1008450214	0695614771	0796069326	103483887	1103414096	0724819594	0789002413	2214212029	0772248262	0844175104	0857812401	0912177796	1341863387	12283594	0965125198	1020339633	1341845426	1268204301	0514093548	0792908922	0534939971	1340459286	0989748766	1006300084	1511850707	1081455912	1095802532	1423582028	2084704389	0578973244	1120961562	0907804039	1188667915	1373479247	1152683291	1603231935	1063993904	0990106056	0838889646	0707422065
L-Methionine	0887109243	0760864093	102019977	1019278193	0907113175	1287094767	0989227709	1287330474	1093767303	1420320714	1049905614	1108713468	1743933459	1198990566	1450499396	10046515	1105180829	0876438825	0788845723	0900718757	0702399434	1100310848	0901275926	0954560052	2777309006	1218403196	1006634113	2330460132	1693104388	0713735507	1036508449	1047567878	16119489	1318187127	1157488716	1142439711	0588993339	0997367005	1126212623	0459916387
L-Phenylalanine	0844860651	0563332729	1107392303	0934202239	0801273173	109741552	0726481185	1494852075	1159399582	1296636088	0979816507	0930743313	1639117155	1094401046	1296745547	082954874	0824030238	0897604898	084785738	0786003077	0744446651	0685938955	0679946229	0812914283	1111089001	109856943	0942315905	1610639297	138883728	0786403507	1032432161	1050234462	1604333307	1489866069	1065829521	1373514921	0627083717	0764539768	1110938134	0411983865
L-Tyrosine	0909246166	0687557431	0934944093	1017602277	1029122244	1165823555	0924308567	1430737253	1362985226	1167435582	0976533983	1007086871	1420416606	1402273956	1311992975	0900277903	1169561554	093238639	0818090413	0985271936	0701005489	0904237448	0916058775	091623331	1294043052	1498275447	1024248638	1654707831	202943437	0763629874	1385890095	1031918269	1688651713	1818318962	141751454	1158061492	0767863528	1049769251	0989489337	0459908378
L-Tryptophan	0796055865	0641689074	1267755556	0761657603	0774263106	1149229495	0922926562	2011475809	1047987707	1376086353	0916795876	0934228473	1580549123	0954863874	1283411322	0906787194	0984473911	0971138232	0885195386	0864363943	070163464	0741224583	077687388	0665737237	095940313	1035036319	0986345128	1833080112	1555339329	0750449383	0928480676	0992476305	1543818603	1585479878	0921167101	1170701595	0622324769	0902138854	1084285502	0340882738
Glutathione	0768922415	0559520392	1254861372	073031231	0611669811	1037554632	1085456374	1355824066	1078140448	070056026	0872907554	0947300666	1565641882	1107244869	095693212	0790203831	0596584142	0869078896	0687106133	0478303637	0158124962	0445140536	0690835432	0818351037	1928188285	081469461	093694808	1335931878	1554576647	1338691253	1158114144	1140832466	2068404121	1770733067	1517055127	0505183835	0235380942	0909155355	1362169225	0783474604
Oxidized glutathione	0095789946	0638691587	0378358919	0503461429	0447393508	1114192871	0873219447	0364682943	1272066617	0889103452	2780691896	0856464964	0662954564	07588588	0532301976	0761060029	041927642	0544303572	0809528567	1048942533	0653653609	0208590854	0477434946	1041286696	1429124791	0739881702	0980756221	1460701364	0814837632	0743838809	148306767	1303611189	1972159301	0976559876	0616692607	044369386	081676634	0678616254	0786600574	0325871886
S-Adenosylhomocysteine	0917901335	0940501707	1408715342	0858766228	1075497587	1289218877	1185978016	1700031563	1004755574	0377432359	0826481556	0553310104	0238284585	1388936489	0447273328	1114119086	1293101136	1202701316	0927298962	0910878224	027784364	0958272545	1268145538	1237599302	1482734466	1474596579	1158709082		1671510931	1089417237	1701982001	1499128057	171670973	2578414163	1493978623	1055171334	0546890886	160036382	0915393771	0912822703
Acetylglycine	0793824067	0545959192	1249844431	0777545093	0736995731	1143449299	0853368782	23154353	1102432948	1293666483	0882078598	0869632286	1606104016	1032457198	1267012025	0893519069	0854748192	09768688	0865201058	084579436	0602358144	0667376553	0689704784	0604914397	0931357264	1005119206	1023224555	1713119562	1722789485	076941365	0797432356	1028421144	1509272921	1967287546	088863868	1213408145	0580775421	0794205175	1056878537	0310957641
Pyroglutamic acid	1274874525	1218732396	0768273432	107784367	0724389807	1299871905	1831601196	101401159	0960305135	1195560578	1196070312	1833254403	0869264735	102041841	0989189278	1170416848	1988271974	0687657788	1026959378	0783411358	0822977453	0797733536	0676109511	0855433204	0913723299	1107095307	1083395377	1218329271	1213148055	087354983	1087378713	1112369104	1156871274	1180843362	0896553846	1354737243	0744591866	0788955452	1004597415	0707513449
3-Hydroxyglutaric acid	0847659628	0940888555	0622118174	0897676308	0922559365	1557203663	0829703709	108504803	1239679997	1388279723	1134188147	0694926512	093751478	0671047099	0829687035	1181284821	0639010827	1095449643	1235496421	119027936	1568972823	1096486572	0626254668	0808411297	0600951119	1286472275	1196800794	0894832849	0928136307	0405706172	0762671166	0861909116	0570680074	0647357369	0314199742	1986952938	1218697542	0482082729	0716027634	0152539421
Fructose 1,6-bisphosphate	015956543			0605260207	0216781548	1613266436	059691649	0073867277	3049302918	0436471385	5379967255	0494399634	1840885686	0174188567	0180036914	0855575556	1161822758	2085213279		3393904637	1123313315	0269361186	1874422966	1003508989	192418355	0658844327	0617604158	183411559	4788129955	0442327428	1080136118	0525799894	2010903465	0123422525	027588276	0317865857	4851226459	3032394765	0548941721	0196994166
2-Phosphoglyceric acid	0899171346	0360361822	0356714846	0609826113	0168838813	0740886707	0640755634	0648274873	1654354374	0629707589	1453367602	1098756514	1527344572	1148301484	2533720191	0442267316	0506791156	015319501	0193040744	0090376566	0259284212	0478974358	0224434028	0289018957	2075362327	0404421355	0910671748	3205831882	195695922	0375704895	0173733637	0669959795	2474042056	2602041404	1334050656	4143057318	0231960132	0329968702	0905666392	009210401
ADP	0685278549	0351444403	0382941457	0478216084	0430125873	0889619138	0527861639	0578984722	0985420517	029915841	0991383914	0327958158	1224512117	0392916133	0841967609	0661216267	0198146549	0528710639	0312266998	0542089073	0909066153	0467178813	0642860054	1057505691	1950477887	0775095389	0943288045	2267117387	183591736	0821086902	048778038	0632410148	1823824377	1160843491	1475964042	0908400113	0922746055	0793839226	1014183421	0282877642
Adenosine triphosphate	0702309107	0432961677	0271024932	1204266616	0613315858	0930021922	0531931993	0403578336	1755687977	0623853128	0548013785	0637746424	0395331117	1668913759	0963640751	0660678426	0285874565	0357328524	1120005876	0788305987	1170584535	046401931	0771016894	1176466752	1299395525	1134413557	0888212258	1658541331	1759826182	0901040608	1456374274	1296400451	1887847349	2019914551	1429016819	1004220272	0912482236	1079939756	1153627329	0382469032
Adenosine monophosphate	0687728588	0309059497	0338627021	0195126042	0258722347	0849238372	0335296605	0770053041	050018859	0194919405	1989685474	0137075924	2142913164	0105489117	0570135258	0745047511	0113121521	0536944243	0167154421	0362074624	0912183166	0380215104	0461186971	0957789595	1619760261	0430978096	0948005962	2845673572	1705001541	0831538537	0140418798	025475319	1425168216	0785386005	1357055999	1069461903	0860405176	0530602101	1089531661	024897112
Alpha-D-Glucose	1079178126	0995198266	1150235702	1232057001	1209528819	1081651669	1157699252	1770493987	137722545	1224509492	1101259031	1071548204	1236539632	1179063391	1147287015	1078580885	1148677353	1273409007	0951539265	1020374463	0972800098	1209831701	0927475308	0950748793	1778516049	1553833364	1423200797	126882153	113087562	054860313	108941831	1180731853	0966164431	0867541481	0784464922	1431931821	1062581684	0858287645	0762948312	0695624168
Glucose 6-phosphate	0417906673	0313556669	0644018655	0996999928	0467544244	1264547661	0397665263	0768862051	1410965437	0477756082	1575001911	0605167125	2396587045	0684669318	0865368166	0789076205	036233439	0663649879	0525063916	0790511029	1203561863	0303726906	0501721497	0988035554	1275968264	1021258326	0908699633	0847770806	0837998281	0935242113	0727125794	0921959394	147635415	0742933511	0952513834	1098990826	0901704121	0477280196	0939583509	
L-Ribulose	0805935481	0622646187	0496659982	0311307896	0292147185	0860716059	0898268556	0760017237	0743523043	04138793	1283279788	0767192322	2077695706	0396179133	095514789	0717682674	0306127048	0854668247	0337045806	0419943695	0792434962	0234400246	0152790122	0502674746	1530581554	0513655897	0643384838	1285973435	1062959258	1037073506	0449609496	05618877	1467809707	087096549	0651662046	0880585391	0612282974	0278500305	0931652784	0603791735
D-Ribose 5-phosphate	0839444963	0775492502	0511607706	0363948915	0346950324	0809040434	0944732273	0833170897	0808665009	0455626094	1376582505	0917399235	2252917264	0479783822	0086711282	0771377482	0297336203	0888077464	0340734418	0435564912	0976361387	0287723953	0174956095	0581303976	1300098339	0585902355	0678129226	0905211569	0889796372	0922733973	0527627661	0614237504	145979937	0862254366	0605231564	0906061638	0607140095	0231614954	0938543756	0688907271
NADP	0798137794	053263321	0460832554	0558681357	0644033432	1087486615	0751029453	100483133	1138619696	0734693494	0828781846	0572498899	1106717648	0577090895	0837428917	0867537146	0417414017	0993025021	0440322188	0843926005	095383964	0512567946	0469522741	0862594856	1215826314	0840260757	1060238168	2095213064	187825937	0600461864	056728189	0783367145	1490824735	1117884399	1035592794	088507488	0893371747	0607971505	0817495671	0303526695
NADPH	0668363466	054995505	0453055345	0408896043	0485530113	1174472383	0732136306	0922894836	0849279058	0654773012	0818127671	0491914971	1045228357	0398463027	0738991452	08999905	0319243153	0866759315	0510210659	0817429021	0954206622	0403722753	0311268565	080275027	1026911598	0700498498	088149689	1647108269	149639848	0687800454	0488744182	0850141659	1496616477	1165984481	0855655481	0831399345	0812295805	0445943009	0892918946	0245699454
Succinic acid	0790823953	0813086839	0357870602	0462461423	0602387837	1107737728	1074297744	1902397063	0591101939	0936756572	1482719442	1161179445	0949062185	0505133178	0742652375	1042143529	1248648964	10186945	0702832859	0639964014	0723281546	0505502644	0752473376	0731748836	0958364001	0739405765	1410429354	1167004076	1652025808	1192633379	0702126726	0946081966	1474270966	1791795083	1425879244	054374073	040405909	0837500739	0987133336	0326491141
Malic acid	055080164	05425972	0298502698	0628452559	0336556152	1026615979	0992950272	0769520872	1115150665	0673604296	1113720182	088907617	0926814969	0983414706	0326403224	084743334	0645789371	0670881638	0771605035	0466877405	0401171182	0302125839	0583611523	0774518654	1343948563	0523940955	0897355607	1192074853	1459029861	12729362	1080399828	1364020217	1719635947	221694239	1294676111	0655094598	0342745465	0736728869	1035807067	0431089305
Oxoglutaric acid	0837573996	0956735536	0264112376	0935082749	0915721478	1135182943	1029257534	0878293563	1184701733	1492005258	1169035105	1211713314	0606899608	141364004	1595967942	0971040686	0602357134	0701763746	096327441	1121774405	1345251069	0870049446	0469030041	0590211802	0762418446	1205523946	0863082133	0650003278	071317167	0846339401	1160413403	1137291089	1052648852	1454148235	0428870707	1341079106	1338288001	0397493029	0612966929	0621826878
Fumaric acid	0770029508	0615858437	0276030912	0888670843	042090955	0914567321	1153897901	1043337926	1323356397	0642808901	1062804096	0988654455	1013414136	1400861473	0367275305	0953713315	0983775095	0831264262	0650007419	0419392704	032625454	0452236526	0832514352	0709282131	2217812564	0672707153	0995407793	1490811902	1910652454	1772342515	1247228846	1644503272	2736464562	3051486905	1847320602	0877765237	0363858619	0924903936	1224011534	0622973168
FAD	0903510275	0825497986	1237887484	1028437218	1153879109	1065599249	0603555612	1722601532	0682583491	0933673097	0688958914	056103301	0874328077	098715111	0634416794	1297179671	0766092915	1129861167	0633865143	1101499416	1134949445	1335727975	1492765594	1503788336	1468427013	1383145668	1142452942	0656364223	1388607369	0730123422	086021325	1045651366	1232835918	1426072678	0995948511	1274300126	112216359	1246626493	1016766049	054998829
Guanosine diphosphate	081979939	0524286803	0581805427	0547339549	0646361272	1091624664	0620895522	1011791889	0895222454	0597563714	0831604141	045381016	1129767619	0466288273	0871933942	0872745245	0371175896	0745528241	0380720315	0697450741	0739532327	0558121025	066643008	1074578856	16123162	09081142	1097957978	2300317298	1900948242	0733245006	0562966002	0815120308	1748899248	1434839177	1453260165	0987126987	0876710667	0798589861	1009398	0312062622
Guanosine triphosphate	08704166	0659416215	0407586984	1487895828	1005372292	1019347806	0696476618	0654136463	2033056607	1193091214	0506979627	1027811938	0372908925	2112250564	1101219991	0848073748	0553332663	0567747391	1375163195	1045581174	0870249621	057616758	0856772002	1262820316	1101260439	1462453711	1069362659	1864933905	2080237883	0819603316	2052584561	1863384397	2465727355	2997373338	1444614936	115107969	0966392266	1250979111	1138891734	0440789285
cis-Aconitic acid	0430703275	0532574866	0489005834	0973683498	0594235577	1436478075	0757595424	0929035561	1606823838	0778678349	0847334277	0704966831	0822777938	0968674087	1077207824	0908274214	1089205119	0570168163	0693124743	0749741695	0599185185	0608763441	0702026287	0924604945	1082100007	1139126156	1552338519	0135624466	1519991241	0682663989	0834801961	1718390831	2264267101	1747522871	1151739405	118917325	0604562784	0900188222	1056483688	0137061364
NADH	059239692	0791151326	0270960723	0479369634	1483663875	4173815259	0768772381	0386525307	14319058	0897961698	2434638406	0526751526	0217849699	0257926968	086063375	4205995998	499088389	3771930187	0848832659	3391675595	1186501122	0775970469	1388949289	8653844105	0442153851	1086644175	1578880188	1562065735	3235256911	0571035376	1266457682	0498248099	0831322185	0330632559	0271023543	0543995166	1222880637	2056825258	0569477922	0101589292
NAD	0858461915	0678875062	1112914818	1023148618	0937557943	0856244708	077535848	1214771462	1192281316	1043151433	0809235552	0695922447	0876234527	1010928632	0874399465	086557443	0707290803	0911502516	1046364864	0752902006	0842366752	0973971322	0933964918	1053860545	1065627407	1175424196	1237907903	1253896648	1481099246	0820693798	1015365774	1133259676	1482454918	1518102481	1037650939	1260614251	0858382886	0954903386	1131525817	0403627969
D-Lactic acid	1164397553	0947419333	1383581393	0941941762	0920584323	138936788	1079731354	1441029335	0828337018	1024054528	1100583511	1171109128	1405896553	1009087876	0735783349	0990077404	1118036156	1101302436	1070526042	0863365284	0919394795	1042646724	0797139246	0849524456	1088765742	1224640978	1013105069	0834810398	1102546591	1036424699	0975753007	0967624057	140618885	1159021768	1102742215	1062661241	083747303	0752737955	0717505575	0650152048
5-Methyltetrahydrofolic acid	0895185273	0833968621	2636416674	0660389222	0774193762	0988691804	0960659798	2954735943	0945279252	0986230181	1471824415	0835846618	3135639317	0510785904	1350464449	0560579276	0822574665	1332470634	0539862755	0502343546	0588355731	0901289534	0981518512	0852832022	1067328979	1052864437	1659609071	2104877802	5721066185	050503784	0420121852	0378169606	2372068137	2496463074	2190708327	0513818045	0336425482	0580578832	0424897748	
Hydroxyphenyllactic acid	1163980818	085453551	0782424904	1114633054	1217777043	157007625	0905751683	2180002807	1239414282	1293531056	1255978103	0938302621	1782146103	123256532	1224681203	1062969841	0906256734	1278251605	0879093224	1131037404	0930788715	1103629064	063316392	0940931868	0935970169	1474338366	0905108026	1150562764	203784766	074362892	075507487	0610200259	1191445578	1577974413	0559942022	1655096453	1277212902	042303366	0542148062	0320712366
Trehalose	0490139598	0342030397	099005943	0922189852	0725700288	0382544334	0509256718	1856123395	0601969088	0678534358	0540201189	3359807947	2980451031	1068225696	1155536433	0495178904	1051625926	1235453261	0529092459	080194253	0573552716	0841809548	1411347315	1444954612	1997815452	0974536734	0983870197	157353454	1989950337	0973013391	0977922102	1177734503	2153918547	2165819436	175346806	1127415368	0757298537	1441029947	1150088558	112729152
Sorbitol	1368840944	1231939752	1154072669	0474602038	1044336488	5070291488	0806571215	076505088	0500719649	0556847661	1282451991	1742246515	0948453867	0620850388	0540861822	2375742022	1509195693	1067957451	0691415583	0580791811	1076778604	097475105	049828669	0464707342	073258108	0667908957	1803180644	1052925759	0929412219	0882831611	0787579236	1995319191	1350925896	0555064631	0554056752	0805986115	0889830192	0439965699	0380481102	0322535525
Coenzyme A	0834476643	0665443488	0862867466	0734779985	0642903699	0943273722	1232253388	1091519213	0938773229	0755684525	0631936404	1122898446	2055008296	0702488843	0928504879	0847335315	0706689516	0737696222	038523055	0594132618	0261212443	0586917826	0614830083	0999850969	2425585707	0684313171	0944028489	2661291102	2117323178	0914113779	0595659758	1065625155	3191986483	1736508093	1263284311	1040892603	0453476162	0730325652	1361443532	0423232223
Cytidine	1265297077	0874365184	1073206337	1129004552	108256442	1017679464	0576682541	1037463215	07094382	0715973749	0766416776	0465408926	0636000234	0705324949	0341533255	1156174694	0809323513	0947836225	0896183995	1030510462	1013954565	157904236	2016617733	2044313233	1199585769	110597096	0966225485	1404231199	1930960147	1051835962	049046791	0695301659	131448592	1308734099	1589239068	1104307121	1229441197	1776923328	150248777	063896445
Guanosine	1653540179	0841201711	200932812	2336896761	2363237589	2170232592	083523239	4989017821	1281924331	1620193912	0155694982	076778944	1268538534	2259557821	1463233704	2670618172	1590595476	2088944821	1074884337	1638888384	0710718851	2564506031	2093022309	1826309937	1119816975	2416612809	2485635394	1290859781	2206456981	0390237589	1726889619	2027732817	1403131131	2692921396	0871317372	1276213194	0911765299	1798632115	1235843981	0264857966
Deoxyguanosine	5293209839	120090623	0749334101	1781761225	3780904551	1167274268	1111946347	1932676883	0468303138	0453438352	0034388235	042242281	0079032923	5147036369		1953755717	6802879512	1573238794	3158359059	1244368914	0909143473	420956669	1040700098	3273524915	1324598093	1565654947	3354709215		2256837297	0670866624	2649399127	7366004244	1318820759	1027780612	0915277735	1086267967	1084929823	8350338233	4876262146	301093396
Cytidine monophosphate	065736762	0326993587	0602071197	0359832958	0387540828	0738032218	0370825063	0722707698	0545823679	0288401209	1083380832	0183293836	1758087584	0112952934	0561357623	0683182793	0129922054	0563404302	0155674268	0615590971	2014876325	0733665524	0567369993	1100060581	2065532302	0478841517	0705442735	154632411	1662295041	109092385	0190654526	0416710164	1635668572	0962085522	1020400662	1544385249	1157575459	0498338728	1256269915	04396013
Cytidine triphosphate	1075068956	0577254578	032867198	2062308077	1057033238	0942884003	0539040405	0665757192	1680227404	0701883753	0613750406	0860638924	0427373786	2275368249	101450322	0896244151	0709179015	0438753821	1732291331	0827377785	1049668136	1141004229	1205949052	161356478	1709995563	1066878524	0767518079	1440895283	1827703664	1625885877	1922535725	1438114719	2082474104	3823465095	1453966316	1355506498	1439678671	1339476704	1443721249	0785706754
Uridine 5'-monophosphate	0609259898	0307756539	0598896053	0265028732	0288670633	0837360652	0407188487	0794765506	0538896432	0355923687	121614471	0154352696	1831829711	0096998178	0477308996	0636556474	0134256244	0594946455	0186439434	0397337949	0846993374	0347966764	0434069664	092362767	2537666942	0437696551	0938287455	1947000687	1602925556	1235891594	0176024076	0412585943	1572743208	0824700793	1308663485	094273185	0543560954	0492113674	1185057193	0516768762
Inosine	1410810623	0888789927	1271843826	1772791383	191073112	1371772467	0927950212	2226220686	1584665045	1233962819	0234981368	0915649676	1049353492	1997714942	147894427	1507982697	1169767798	1628175165	1075896554	1196542746	0811331241	143792757	1408833616	1550884472	1119292909	1855895034	1943859143	1302176076	1744131661	0425036498	1849685899	1747883214	127877281	2084774162	1035651758	1215968597	0834975687	1367744745	1064972749	0357117164
Xanthosine	2732899626	109668889	0992081863	1339827385	2520357589	3867208548	11295833	3217399814	0811922896	1903482695	0045193384	0571198735	0676266217	1213475372	145777796	3807164913	1769078049	1897418903	0745477606	1900685534	0582833247	1328431721	2056200628	2848258902	041291125	2338339905	2571501741	1340872634	1864194331	0319177693	0869103091	134791101	0773781254	183762998	0388379962	104745162	0953422185	1838826321	1461770494	0082744408
Uridine diphosphate glucose	052541291	0497993589	0850244136	0734747814	0727579976	0840264201	0680404454	100250147	1002981533	0878095605	0765734236	0826266699	1103474688	1208270634	1038836122	0753362281	0591531235	0874574562	0704061822	080963951	0611336339	0603748936	107033665	0091193774	2823755499	1013328085	0944591689	1566706065	2123057698	153590119	1609352576	1211890491	2567423909	2442101797	1881627803	0667824643	0478392815	1516221413	1157162771	0771032882
ADP-glucose	0663254864	1096350928	1613351699	0938608489	0779975367	1105913623	129128651	1134696537	1055135069	1758854518	0939591276	1146174949	1513765328	1060036474	0984730945	1010082618	0708476118	0790425516	1859274466	0869255414	1499107452	0779893071	0725943158	0229928647	1575334402	1069317031	0824250635	1877758604	1169124993	0765331709	1071233659	1352054657	2452643686	1488207738	0941812386	1066559805	0801770162	0798730537	1135805072	0305487617
Uracil	1453884858	1174446257	1865520262	0221547452	1391383171	1613361952	1141049111	2207756357	0292367353	140905393	0984006392	0466315251	1908759069	0137109478	0759755829	1624813767	1592599962	1976310627	043075446	1676800141	0549958971	0624757029	0447565644	0444640877	1190562803	0907812731	0846620363	0628030525	0887309456	0532856886	0522926667	0543679232	0437249739	0409994259	0625460816	1090905166	0590509586	0514013662	0426683723	0297686188
dGTP	0708398485	0457031981	027408546	1218071687	0627916422	0925675464	0537654969	0399994969	1790757234	0635747294	0552023437	064623967	0408697749	1710145019	0961646269	0669828222	0281459565	0367557795	1179817826	0788987119	116539519	0465707535	0774327092	1189981346	13124734	1170468481	0899771545	1733652604	1746991778	0904565836	1496150159	1325916805	1972343159	2071414774	1446281277	1001644485	0899393502	1069589673	1171490416	0397038898
Folic acid	0778908036	1006245993		0979317876	0774421618	1265971297	2021616416	1247687701	11934463	1743209922	0676828881	2373233768	0281412	1481402744	1630815016	0706580448	3229367955		0651881364	0921232163	0860094192	0963689264	0580471632	0436445967	0848319218	1957816221	1558302004	1012658103	1050768416	0497163048	132756736	1577759959	1146654735	1337348244	0723290627	1670863897	0748553624	0702573506	0606942718	049427664
Pantothenic acid	0947243198	0895161535	016236349	076084801	0675736098	1311135954	1276818169	0401303551	1020687136	108198718	1360115034	1552934268	0826047881	1401049291	1557458807	0916946898	1914185129	0211816405	0886855985	079267672	0906209383	0762464192	0475862993	0546820855	1012502795	1339601085	0957893211	1043536383	0970084686	0800620347	1650268807	1250545338	1293511317	1343501606	0836965989	1928017495	0880010155	0624326693	0667991254	0491715755
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	HMDB	KEGG
L-Leucine	HMDB00687	C00123
L-Asparagine	HMDB00168	C00152
L-Aspartic acid	HMDB00191	C00049
L-Glutamine	HMDB00641	C00064
L-Lysine	HMDB00182	C00047
L-Methionine	HMDB00696	C00073
L-Phenylalanine	HMDB00159	C00079
L-Tyrosine	HMDB00158	C00082
L-Tryptophan	HMDB00929	C00078
Glutathione	HMDB00125	C00051
Oxidized glutathione	HMDB03337	C00127
S-Adenosylhomocysteine	HMDB00939	C00021
Acetylglycine	HMDB00532
Pyroglutamic acid	HMDB00267	C01879
3-Hydroxyglutaric acid	HMDB00428
Fructose 1,6-bisphosphate	HMDB01058	C00354
2-Phosphoglyceric acid	HMDB00362
ADP	HMDB01341	C00008
Adenosine triphosphate	HMDB00538	C00002
Adenosine monophosphate	HMDB00045	C00020
Alpha-D-Glucose	HMDB03345	C00267
Glucose 6-phosphate	HMDB01401	C00092
L-Ribulose	HMDB03371	C00310
D-Ribose 5-phosphate	HMDB01548	C00117
NADP	HMDB00217	C00006
NADPH	HMDB00221	C00005
Succinic acid	HMDB00254	C00042
Malic acid	HMDB00744	C00711
Oxoglutaric acid	HMDB00208	C00026
Fumaric acid	HMDB00134	C00122
FAD	HMDB01248	C00016
Guanosine diphosphate	HMDB01201	C00035
Guanosine triphosphate	HMDB01273	C00044
cis-Aconitic acid	HMDB00072	C00417
NADH	HMDB01487	C00004
NAD	HMDB00902	C00003
D-Lactic acid	HMDB01311	C00256
5-Methyltetrahydrofolic acid	HMDB01396	C00440
Hydroxyphenyllactic acid	HMDB00755	C03672
Trehalose	HMDB00975	C01083
Sorbitol	HMDB00247	C00794
Coenzyme A	HMDB01423	C00010
Cytidine	HMDB00089	C00475
Guanosine	HMDB00133	C00387
Deoxyguanosine	HMDB00085	C00330
Cytidine monophosphate	HMDB00095	C00055
Cytidine triphosphate	HMDB00082	C00063
Uridine 5'-monophosphate	HMDB00288	C00105
Inosine	HMDB00195	C00294
Xanthosine	HMDB00299	C01762
Uridine diphosphate glucose	HMDB00286	C00029
ADP-glucose	HMDB06557	C00498
Uracil	HMDB00300	C00106
dGTP	HMDB01440	C00286
Folic acid	HMDB00121	C00504
Pantothenic acid	HMDB00210	C00864
METABOLITES_END
#END