#METABOLOMICS WORKBENCH tverkerke_20240429_123306 DATATRACK_ID:4799 STUDY_ID:ST003264 ANALYSIS_ID:AN005348 PROJECT_ID:PR002026
VERSION             	1
CREATED_ON             	June 17, 2024, 5:26 pm
#PROJECT
PR:PROJECT_TITLE                 	SLC25A48 controls mitochondrial choline import and metabolism
PR:PROJECT_SUMMARY               	Choline is an essential nutrient for cellular metabolism, including the
PR:PROJECT_SUMMARY               	biosynthesis of phospholipids, neurotransmitters, and one-carbon metabolism. A
PR:PROJECT_SUMMARY               	critical step in choline catabolism is the mitochondrial import and synthesis of
PR:PROJECT_SUMMARY               	choline-derived methyl donors, such as betaine. However, the underlying
PR:PROJECT_SUMMARY               	mechanisms and the biological significance of mitochondrial choline metabolism
PR:PROJECT_SUMMARY               	remain poorly understood. Here, we report that a previously uncharacterized
PR:PROJECT_SUMMARY               	mitochondrial inner-membrane protein, SLC25A48, controls mitochondrial choline
PR:PROJECT_SUMMARY               	transport and catabolism in vivo. We show that SLC25A48 is highly expressed in
PR:PROJECT_SUMMARY               	brown adipose tissue and is required for whole-body cold tolerance,
PR:PROJECT_SUMMARY               	thermogenesis, mitochondrial respiration, and mitochondrial membrane integrity.
PR:PROJECT_SUMMARY               	Choline uptake into the mitochondria via SLC25A48 facilitates the synthesis of
PR:PROJECT_SUMMARY               	betaine and purine nucleotides, whereas loss of SLC25A48 resulted in increased
PR:PROJECT_SUMMARY               	production of reactive oxygen species and imbalanced mitochondrial lipids.
PR:PROJECT_SUMMARY               	Notably, human cells carrying a single nucleotide polymorphism on the SLC25A48
PR:PROJECT_SUMMARY               	gene and cancer cells lacking SLC25A48 exhibited elevated oxidative stress and
PR:PROJECT_SUMMARY               	impaired cell proliferation. Together, the present study identified SLC25A48 as
PR:PROJECT_SUMMARY               	a mitochondrial carrier that mediates choline catabolism and plays a critical
PR:PROJECT_SUMMARY               	role in mitochondrial function and cell survival.
PR:INSTITUTE                     	Beth Israel Deaconess Medical Center
PR:LAST_NAME                     	Verkerke
PR:FIRST_NAME                    	Anthony
PR:ADDRESS                       	330 Brookline Avenue, Boston, Massachusetts, 02215, USA
PR:EMAIL                         	averkerk@bidmc.harvard.edu
PR:PHONE                         	7159231910
#STUDY
ST:STUDY_TITLE                   	SLC25A48 controls mitochondrial choline import and metabolism
ST:STUDY_SUMMARY                 	Choline is an essential nutrient for cellular metabolism, including the
ST:STUDY_SUMMARY                 	biosynthesis of phospholipids, neurotransmitters, and one-carbon metabolism. A
ST:STUDY_SUMMARY                 	critical step in choline catabolism is the mitochondrial import and synthesis of
ST:STUDY_SUMMARY                 	choline-derived methyl donors, such as betaine. However, the underlying
ST:STUDY_SUMMARY                 	mechanisms and the biological significance of mitochondrial choline metabolism
ST:STUDY_SUMMARY                 	remain poorly understood. Here, we report that a previously uncharacterized
ST:STUDY_SUMMARY                 	mitochondrial inner-membrane protein, SLC25A48, controls mitochondrial choline
ST:STUDY_SUMMARY                 	transport and catabolism in vivo. We show that SLC25A48 is highly expressed in
ST:STUDY_SUMMARY                 	brown adipose tissue and is required for whole-body cold tolerance,
ST:STUDY_SUMMARY                 	thermogenesis, mitochondrial respiration, and mitochondrial membrane integrity.
ST:STUDY_SUMMARY                 	Choline uptake into the mitochondria via SLC25A48 facilitates the synthesis of
ST:STUDY_SUMMARY                 	betaine and purine nucleotides, whereas loss of SLC25A48 resulted in increased
ST:STUDY_SUMMARY                 	production of reactive oxygen species and imbalanced mitochondrial lipids.
ST:STUDY_SUMMARY                 	Notably, human cells carrying a single nucleotide polymorphism on the SLC25A48
ST:STUDY_SUMMARY                 	gene and cancer cells lacking SLC25A48 exhibited elevated oxidative stress and
ST:STUDY_SUMMARY                 	impaired cell proliferation. Together, the present study identified SLC25A48 as
ST:STUDY_SUMMARY                 	a mitochondrial carrier that mediates choline catabolism and plays a critical
ST:STUDY_SUMMARY                 	role in mitochondrial function and cell survival.
ST:INSTITUTE                     	Harvard Medical School
ST:LAST_NAME                     	Verkerke
ST:FIRST_NAME                    	Anthony
ST:ADDRESS                       	330 Brookline Avenue, CLS 730
ST:EMAIL                         	averkerk@bidmc.harvard.edu
ST:PHONE                         	7159231910
#SUBJECT
SU:SUBJECT_TYPE                  	Mammal
SU:SUBJECT_SPECIES               	Mus musculus
SU:TAXONOMY_ID                   	10090
SU:GENDER                        	Male
#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           	-	Serum_1	Genoptye:Control | Sample source:Serum	RAW_FILE_NAME=Serum_1.RAW
SUBJECT_SAMPLE_FACTORS           	-	Serum_2	Genoptye:Control | Sample source:Serum	RAW_FILE_NAME=Serum_2.RAW
SUBJECT_SAMPLE_FACTORS           	-	Serum_3	Genoptye:Control | Sample source:Serum	RAW_FILE_NAME=Serum_3.RAW
SUBJECT_SAMPLE_FACTORS           	-	Serum_4	Genoptye:Control | Sample source:Serum	RAW_FILE_NAME=Serum_4.RAW
SUBJECT_SAMPLE_FACTORS           	-	Serum_5	Genoptye:Control | Sample source:Serum	RAW_FILE_NAME=Serum_5.RAW
SUBJECT_SAMPLE_FACTORS           	-	Serum_6	Genoptye:Control | Sample source:Serum	RAW_FILE_NAME=Serum_6.RAW
SUBJECT_SAMPLE_FACTORS           	-	Serum_7	Genoptye:Control | Sample source:Serum	RAW_FILE_NAME=Serum_7.RAW
SUBJECT_SAMPLE_FACTORS           	-	Serum_8	Genoptye:Control | Sample source:Serum	RAW_FILE_NAME=Serum_8.RAW
SUBJECT_SAMPLE_FACTORS           	-	Serum_9	Genoptye:SLC25A48-KO | Sample source:Serum	RAW_FILE_NAME=Serum_9.RAW
SUBJECT_SAMPLE_FACTORS           	-	Serum_10	Genoptye:SLC25A48-KO | Sample source:Serum	RAW_FILE_NAME=Serum_10.RAW
SUBJECT_SAMPLE_FACTORS           	-	Serum_11	Genoptye:SLC25A48-KO | Sample source:Serum	RAW_FILE_NAME=Serum_11.RAW
SUBJECT_SAMPLE_FACTORS           	-	Serum_12	Genoptye:SLC25A48-KO | Sample source:Serum	RAW_FILE_NAME=Serum_12.RAW
SUBJECT_SAMPLE_FACTORS           	-	Serum_13	Genoptye:SLC25A48-KO | Sample source:Serum	RAW_FILE_NAME=Serum_13.RAW
SUBJECT_SAMPLE_FACTORS           	-	Serum_14	Genoptye:SLC25A48-KO | Sample source:Serum	RAW_FILE_NAME=Serum_14.RAW
SUBJECT_SAMPLE_FACTORS           	-	Serum_15	Genoptye:SLC25A48-KO | Sample source:Serum	RAW_FILE_NAME=Serum_15.RAW
SUBJECT_SAMPLE_FACTORS           	-	Serum_16	Genoptye:SLC25A48-KO | Sample source:Serum	RAW_FILE_NAME=Serum_16.RAW
#COLLECTION
CO:COLLECTION_SUMMARY            	Standard chow fed mice were fasted for four hours prior to serum or tissue
CO:COLLECTION_SUMMARY            	collection.
CO:SAMPLE_TYPE                   	Serum
#TREATMENT
TR:TREATMENT_SUMMARY             	Samples are from wild-type or SLC25A48-KO male mice fed a standard chow diet.
TR:TREATMENT_SUMMARY             	Mice were fasted for four hours prior to sample collection.
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	10 µL serum was mixed with 90 µL extraction solvent of methanol: acetonitrile:
SP:SAMPLEPREP_SUMMARY            	water 40: 40: 20 at -20 ˚C, and then vigorously vortexed. All samples were then
SP:SAMPLEPREP_SUMMARY            	conditioned to -4 ˚C, and centrifuged at 16,000 rpm/min. The supernatant was
SP:SAMPLEPREP_SUMMARY            	transferred to LC-MS tubes for analysis.
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_SUMMARY        	Waters XBridge BEH Amide XP Column (150 x 2.1mm, 2.5um) with guard column (5mm x
CH:CHROMATOGRAPHY_SUMMARY        	2.1mm, 2.5 µm)
CH:CHROMATOGRAPHY_TYPE           	HILIC
CH:INSTRUMENT_NAME               	Thermo Vanquish
CH:COLUMN_NAME                   	Waters XBridge BEH Amide XP (150 x 2.1mm, 2.5um)
CH:SOLVENT_A                     	95% Water, 5% Acetonitrile; 10 mM ammonium acetate and 10 mM ammonium hydroxide
CH:SOLVENT_B                     	20% Water, 80% Acetonitrile; 10 mM ammonium acetate and 10 mM ammonium hydroxide
CH:FLOW_GRADIENT                 	0 - 3 min, 100% B; 3.2 - 6.2 min, 90% B; 6.5 - 10.5 min, 80% B; 10.7 - 13.5 min,
CH:FLOW_GRADIENT                 	70% B; 13.7 - 16 min, 45% B; and 16.5 - 22 min, 100% B
CH:FLOW_RATE                     	0.3 mL/ min
CH:COLUMN_TEMPERATURE            	4˚C
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:INSTRUMENT_NAME               	Thermo Q Exactive HF
MS:INSTRUMENT_TYPE               	Orbitrap
MS:MS_TYPE                       	ESI
MS:ION_MODE                      	UNSPECIFIED
MS:MS_COMMENTS                   	The mass spectrometry used was Q Exactive HF (Thermo Fisher Scientific, San
MS:MS_COMMENTS                   	Jose, CA), and scanned from 70 to 1000 m/z with switching polarity. The
MS:MS_COMMENTS                   	resolution was 120,000. Metabolites were identified based on accurate mass and
MS:MS_COMMENTS                   	retention time using an in-house library, and the software used was EI-Maven
MS:MS_COMMENTS                   	(Elucidata, Cambridge, MA).
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	Peak area
MS_METABOLITE_DATA_START
Samples	Serum_1	Serum_2	Serum_3	Serum_4	Serum_5	Serum_6	Serum_7	Serum_8	Serum_9	Serum_10	Serum_11	Serum_12	Serum_13	Serum_14	Serum_15	Serum_16
Factors	Genoptye:Control | Sample source:Serum	Genoptye:Control | Sample source:Serum	Genoptye:Control | Sample source:Serum	Genoptye:Control | Sample source:Serum	Genoptye:Control | Sample source:Serum	Genoptye:Control | Sample source:Serum	Genoptye:Control | Sample source:Serum	Genoptye:Control | Sample source:Serum	Genoptye:SLC25A48-KO | Sample source:Serum	Genoptye:SLC25A48-KO | Sample source:Serum	Genoptye:SLC25A48-KO | Sample source:Serum	Genoptye:SLC25A48-KO | Sample source:Serum	Genoptye:SLC25A48-KO | Sample source:Serum	Genoptye:SLC25A48-KO | Sample source:Serum	Genoptye:SLC25A48-KO | Sample source:Serum	Genoptye:SLC25A48-KO | Sample source:Serum
Glycine	1225430	2320490.75	1779886.62	2194564.25	2097928.5	1515518	1748514.12	985511.19	1433609.62	1154625	2000670.88	1662599.5	3147505	1508015.38	1857567.12	1341462.5
Pyruvate	23924456	32530288	27897256	28749728	23914318	33709308	45257248	16863430	20940762	30035338	37011460	30044382	28872898	28634270	23025056	33156634
Alanine	6153598.5	12505721	5792692	6671501.5	7369422.5	6649625.5	6900876	4180097.75	6809190	6305382.5	6944698.5	7618906.5	10712536	5455919.5	6637168	4714727.5
Lactate	897720512	1421378560	740421120	1074212992	942787392	986395456	944792768	494441504	917643456	907844096	776189376	1173278336	1133771904	529590912	641828544	932300224
Acetoacetate	2522249.75	1199765.38	3614415	2821719.75	1881129.62	1303955	1545122	3027213	1248155.5	1598518.12	4179529.25	2082808.38	1644289.62	3434839.75	2751486.75	1855312.38
N-Formylglycine	48213.83	194062.7	40914.44	39255.39	60000.55	53730.72	87635.46	44512.47	47868.86	67911.65	80048.59	45528.39	40386.44	38875.89	54144.69	42294.77
3-Hydroxybutyric acid	36672364	17791076	23687864	38528308	20304638	15974096	12474229	27003798	15072616	13457024	33158678	24499342	21835544	25903686	29239418	27354544
3-hydroxyisobutyric acid	7627331.5	7363322.5	6746913.5	12512789	9473919	12315915	11506080	6742092	3978191	6218531.5	10984764	8416761	9533439	8506153	11908183	7660634.5
Serine	5331298.5	8674439	5543226	5900095.5	5856850.5	4595102	4689342.5	4012436.25	5545843	4290497.5	7951633.5	5727254.5	8747435	3444635.75	5220254.5	3510365.75
Glycerate	360339.25	557153.06	499962	520945.5	510668.09	609595.06	804318.06	435740.59	412617.5	556681.31	495700.12	521573.91	500766.38	531999.12	584590.69	653914.44
Fumarate	902034.31	3514500.75	1428043.5	1571090.38	1614615.5	2330940.75	2119228	1109031.38	1925452	1407355	1077858	1222593.12	2365343	1292742.62	1533362.38	1769987.38
3-methyl-2-oxobutyrate	9568652	8155066.5	8929957	10307959	9992607	9297685	9828153	7790877.5	8306737.5	12021008	9666099	8345210.5	9098435	7309150	7939652	8579067
N-Acetylglycine	9592261	7316222	6987802.5	11737080	9162757	8158904	5969186	4704361.5	8459385	6559688	9402489	8637463	7870204	6130729.5	6163034.5	6921804.5
Guanidineacetic Acid	20098.93	34530.57	13606.94	13946.6	22800.01	25237.63	29815.38	17543.12	19925.82	22186.01	36279.94	27979.98	42039.3	41619.27	43552.34	26750.56
Valine	5599345.5	9047671	9656912	8440485	9836693	8965237	8987136	5674174.5	6655985.5	7795145.5	8341627.5	8559016	7982160	4592457.5	8133518.5	5890592
Succinic acid	14138803	48744908	12442873	27875234	30114214	24029672	22363118	10312740	26148592	22740890	11975687	37296000	37731612	8881404	16863382	24239962
Taurine	26588304	34249612	22826010	26014742	29387550	24163808	21871486	15066304	29291728	29675080	24251014	29779742	26878992	17514542	24573850	19289930
Thymine	83460.62	225422.38	102881.38	105111.52	69282.7	167029.78	162292.61	169424.97	82425.02	40182.16	161259.8	67932.91	152718.86	117783.07	232642.58	76180.2
Pyroglutamate	9123253	7776074	7554787.5	7156044	8293232	5751000	4901640	4417456.5	9339349	7099004.5	6469894	7471710.5	6775626.5	4530446.5	6595135.5	3629247.25
N-Acetyl-L-alanine	337069.12	385219.34	202437.92	257536.48	227577.12	290032.59	348687.22	161349.89	241962.61	235993.3	378783.5	469202.62	380565.75	231084.2	388221.12	163993.31
trans-4-Hydroxy-L-proline	445262	576729.81	309581.59	476889.41	436664.72	410271.25	480387.22	175246.92	449541.12	257288.7	380943.25	589785.12	501984.25	167291.72	233364.55	216247.39
Isoleucine	4214249	7737926.5	7358188.5	6041828.5	7193002.5	6932341.5	5965669.5	4644330.5	5509638.5	5511961.5	6026534	6737512	6517610	3570500	5670576	5095492.5
Leucine	8779802	13656835	12559192	11101337	13431016	12752152	11121448	8564304	10370985	10059828	10520279	13000497	11250073	6355056	10989605	8896201
Oxaloacetate	14577.54	23849.82	21438.47	18848.35	22459.9	37052.34	45562.31	18445.49	23555.29	25985.62	23666.31	14360.56	25823.92	25664.81	34176.66	20392.23
Ethylmalonic acid	2293255.5	2432652.75	2538425.25	2409474.75	2752226.25	3473949	3555864.75	2589632.5	2168420.25	2386665.75	1946281.38	2351958.75	2119108.25	2157073.75	1913601.38	2676817
3-Ureidopropionic acid	81978.09	118152.93	74913.9	77788.84	45314.65	86564.9	136633.09	32537.33	47019.14	53353.43	117470.63	200502.55	86961.38	69961.62	254413.75	75857.89
Asparagine	871579	2918424.75	1272046.5	1174382.62	1080888.38	1119312.88	1094632.62	979728	1016456.31	867116.5	2998925.75	1258366.62	3642845.25	1655290.88	2346534	872012.44
Aspartate	217564.08	227596.7	154832.52	206276.67	226384	208637.83	173988.7	102150.34	206285.69	194993.83	238941.89	284982.53	319341.53	125656.98	245013.45	109104.31
Malate	9701411	52811028	14138669	15596697	16376605	27173358	27055382	9535983	20698376	14931508	9744967	13066393	29543450	12080947	16399649	18837066
Urocanate	1531747.62	939215.31	900431	962132.69	811830.81	802237.19	615655.19	351802.41	1299889.38	789706.31	1020012	1075989.25	1051626.38	250567.14	610830.19	220915.83
O-Phosphoryethanolamine	302262.72	528164.25	176309	248628.48	257751.39	212770.06	162610.2	77703.6	312803.66	212841.23	302682.28	343235.94	303688.47	98512.26	107525.59	83607.98
3-Methylglutaconate	5276640	5789570	5847673.5	5385602	6439102	7938338	8724076	6165042	4921175	5533553.5	4290568	5392402.5	4890424.5	4898126.5	4232348.5	6423336
Alpha-Ketoglutarate	6251647.5	18255466	13521188	14132912	11104916	23177312	26409976	12729987	11365225	13553792	13728721	6021470.5	19614054	18235354	18876146	15825816
Glutamate	2680079	4912268.5	2018647.62	3146857	2968554.25	2506899	2055930.12	1341440.88	3009893.25	2607410.75	2967084	3708976.25	4907071.5	1666096.12	3167050.25	2084849.12
N-Acetyl-serine	1165878.5	1204946.12	1062298.75	1430260.88	1650429.12	1174123.38	1183712.5	577451.81	1058014.12	1032934.19	859041.81	1200385.38	849126.69	727103.25	976940.06	743006.31
Citramalate	1104728.38	2478533.75	1562377.38	1644900	1315329	2284506.75	3142481.75	1393061.38	1413970.62	1606573.5	1413222.12	1228067.5	1574182.62	1654811	1876571.62	1843224
Orotate	654942.69	811377.94	763567.81	610592.94	834607.56	1089270.38	1032941.44	489485.25	648208.06	992451.75	617046.25	576840.69	542793.69	728707.19	1000840	563333
Dihydroorotic acid	14745.04	25319.97	29689.14	19703.33	32490.88	45448.31	31041.97	25541.58	29339.17	24229.37	25659.69	20282.52	15174.39	23807.57	38434.71	21477.66
Allantoin	5925817.5	7731043.5	7679949.5	5470880.5	5706972	9248894	10473631	6033150	6010923.5	6743111.5	6018844	7373140.5	5046896	8069209.5	8892280	6967304
N-Methyl-L-glutamate	349664.53	328146.25	209298.58	516453.59	339914.66	476935.09	437761.75	297902.22	183058.83	190942.56	198281.12	201139.25	162587.86	124443.31	132597.38	267322.97
3-Hydroxy-3-methylglutarate	1402678.38	1852723.62	1242059.12	1841912	1345992.12	2211973	2536256.75	1389408.38	1089059.88	1329091.62	1548178.62	1782844.12	1338009.25	1114226.75	1338479.12	1398627.12
Fucose	1121395.75	524810.31	1452206.12	1220336.38	1685060.62	1307600.88	1639748.62	2077502.5	1113104.75	1428574	609797.38	1136895.38	715942	1101402.88	1401391.12	1615546.38
Phenylalanine	2507672.25	3729840.25	3185434	2821987.25	3446971.75	3332661.25	3258231.25	2584729.25	2717704	3063360	4195388	3206138	4279715.5	3342051	4798357.5	1951212.5
Uric acid	4451808.5	5107571.5	499535.41	1271242.38	2224630.25	829647.69	1619543	219580.17	1112799	2280300	1018536.31	3664274	3079926	684118	1950898.62	907921
Dihydroxyacetone phosphate	88592.65	91344.43	22648.88	44025.89	84176.47	20092.75	17403.6	7603.6	94895.56	51146.78	27323.55	67395.88	42831.11	12813.98	14308.85	2006.27
Glycerol 3-phosphate	467948.91	807194	277176.66	376559.91	480270.91	321390.78	309837.44	171527.17	428914.28	376448.03	311903.16	471544.97	366503.75	182570.17	230927	210634.94
N-Acetyl-Leucine	2714885.25	4113435	2514189.75	4458561.5	3990105.25	4457171.5	3594926.75	1701971	1976151.5	2287499.25	4142412.25	2850412.25	3806259	2312465	2242724.25	2229862
cis-aconitic acid	3517562.25	5087760.5	4619357.5	4163077.75	4162052.25	7185108	9226373	5376533.5	3617632	4686885.5	4464114.5	3282885.75	4762702.5	7677123.5	6421600	7468588.5
N-Acetyl-aspartate	533338.31	976078.31	413635.47	461905.91	472211.03	666747.25	756926	327612.06	575735.75	448517.28	417028.16	543839.19	503195.72	274254.22	274005.81	384883.34
Citrulline	1242398.5	1893332.5	2720482.75	1580101.12	1811602.62	2870878.75	3090268.75	1623647.88	1846932.62	1865087	2288515.75	1718975.62	2211793	2755493.5	2800108	1890104.12
Hippuric acid	612574	652641.94	478462.97	318240.66	666510.19	98583.51	122948.71	573175.19	1618303.62	1026492.19	199356.11	798381.5	166398.06	880649	495094.59	638959.56
Glucose	98359744	107298728	108691840	101887104	121513160	154507184	165149392	115910848	90478568	102045800	78880976	98476648	88432344	90895616	78457672	120454728
Tyrosine	2301219.25	5265264.5	2624278	2652532	3158636.75	2715542	2476331.75	2137834.25	3285070.75	2357479.5	3921933	3287822	4599758	2710961	3251220.75	2010534.12
Homovanillic acid	170010.55	500837.03	158331	185026.02	225734.8	336230.72	438736.03	124381.46	212647.33	236205.92	281226.72	184795.33	302965.91	261720.75	285726.84	144325.05
Galactitol	400126.03	636148.31	435269.91	414641.62	494715.09	488169.97	522279	429685.78	447525.62	425463.59	360434.5	363146.16	334037.66	468102.66	431392.5	427845.09
Acetylglutamine	550170.56	376259.66	516090.12	722996	684678.69	533066.25	560120.94	300876.03	674198.06	556116.19	335291.53	534032.62	326926.41	306056.09	487429.84	493343.5
N-Acetyl-glutamate	100903.24	193918.58	179150.83	220501.69	272887.88	340172.22	331409.88	180080.23	138573.98	219881.83	115307.04	127476.88	172484.27	129828.26	136901.42	166013.67
Acetylmethionine	78392.34	262462.12	58968.48	100081.96	103457.91	160847.45	138754.09	56145.41	89899.78	76554.69	104687.76	95068.26	168913.44	82884.74	92618.34	71000.46
Citrate	4620551.5	11191652	6900024	6705881.5	7464897.5	18138490	18594520	6135952.5	5706087.5	6878994.5	5321565.5	4416152.5	8351912	13832748	12706925	6529628
Glucuronic acid	1325324.38	1408714.62	1267122.88	1285396.12	1209967.12	1460412	1488992.5	737349.25	1544210	1164259.62	1216232.12	1214720.38	1014119.31	1120197	1014379.75	1131646.88
methyl beta-D-galactopyranoside	1167542.5	593331.56	831213.81	1088106.38	546125.19	506856.75	388783.91	815208.69	499956	382458	1068143	834470.44	687408.31	832814.94	913430.06	780667.5
Gluconate	2515087.75	2713027.75	1966528	4018402	3364880.75	1993261.62	2102066.75	1060445.38	2481401.75	1399160.38	2261128.25	2666093	2883080	1471063.12	4325328.5	1876996.62
Sebacic acid	203929.38	162822	68638.34	136882.31	58723.98	67136.51	54711.86	46612.44	54857.7	31189.93	83630.66	83254.37	73078.95	70343.97	37530.71	109734.87
Tryptophan	3733069.25	4411570.5	4727177.5	5203845.5	5819418	6400438	6967060	5841224	3152774	5975403.5	4548122.5	4166344.75	5797118.5	5268210	5636036.5	5350958
Indolelactate	312469.25	603230.12	249762.98	274682.66	382276.66	255861.05	279295.38	167482.62	536257.56	378880.72	358558.28	304867.62	303441.09	537652.25	436227.34	197873.3
N-Acetyl-L-phenylalanine	307831.38	2095307.38	454455.78	310185.88	473452.47	554976.56	603703.19	231347.3	458314.12	472084.09	985832.5	392099.09	1008785.19	349529.72	729680.69	316773
O-Succinyl-L-Homoserine	51160.7	73517.99	44165.34	90115.98	59867.32	94273.3	51500.14	27744.17	60668.28	49878.52	71282.17	32923.75	64445.75	44757.45	28250.22	71649.15
Pantothenate	367060.41	931434	565300.12	546927.94	560214.56	713700.69	802645.19	416651.22	423902.5	471033.75	561391.31	732594.81	793754.19	375265.38	854803	404910.62
Ribose 5-phosphate	493323.53	429084.03	62733.55	182329.67	594211.69	289693.22	264264.03	75188.3	583536.19	310266.78	125491.62	444714.22	321156.78	254640.8	445943	40013.61
Thymidine	192950.88	420500.41	253233.55	170481.12	153422.58	391218	332519.38	388851.62	163361.34	84503.68	285257.72	160751.77	272531.53	245595.69	471564	187171.55
Uridine	29531	43132.05	16693.51	18255.05	42266.29	112084.94	69197.74	66669.1	29546.74	34403.98	34692.07	49507.57	32812.76	49079.88	106998.09	98459.04
N-acetyl-L-tryptophan	83566.93	530202.19	107815.03	98458.74	157559.78	157496.55	204760.75	88811.98	78870.88	133078.48	224321.39	89668.59	305212.75	189318.8	292428.84	189772.08
Fructose 6-phosphate	47785.34	76821.95	21284.17	37632.68	41597.48	33719.92	25013.68	8992.58	44806.36	36299.49	30456.22	45396.88	42563.3	10995.25	11846.39	12309
Glucose 6-phosphate	200271.62	296741.16	78444.79	164376.45	149209.98	111375.15	89306.88	31555.79	181336	150877.94	105574.09	204367.58	142921.75	41936.84	44722.05	55730.64
Retinyl acetate	27299360	30862502	43508460	34551052	32907666	38829196	40793908	25487680	22685274	30390882	44482060	27517336	39823636	40602040	37562444	24236080
Betaine	150720336	179216256	99782936	110131288	110728552	69922464	70524712	70099368	69646440	48250060	69457424	66733348	78842072	44748132	48493872	60712924
Choline	147370800	166160112	124263832	132213336	133810240	115981672	121061016	73866552	162337472	176281328	176786432	186150976	195075408	124340280	151825152	128980000
Dimethylglycine	1195022.62	756287.25	792463.69	506627.09	793730.44	504416.09	814380.56	674655.5	89184.94	156687.56	80740.52	49871.41	98507.41	257124.2	157207.27	311295.91
Sarcosine	5447817.5	9784253	4712854	5537574	6089050.5	5449271.5	5720657.5	4096325.25	1759960.62	5382379.5	5980239.5	6162574.5	8724835	4933403.5	5275107.5	4462016
Hypotaurine	445451.59	673168	353752.75	472220.47	372704.66	189130.38	144556.77	57708.33	561820	370022.97	588793.81	430296.75	754978.5	312307.34	382263.03	161468.12
histamine	3169154.75	5855816	3027839	2826633.75	5420263.5	4082966	3236879.25	959138.69	5987428	7766994.5	8214120	5680303.5	5254596	1574457.38	1788937	2893475.75
Proline	13955353	25599598	16111199	15108997	15001525	15523283	16145757	13144595	13554392	11006251	23010054	16715611	27074522	16045376	19758994	13544016
Nicotinamide	617399.31	412715.97	317271.19	458289.34	359205.84	235049.83	241898.08	193939.62	508137.84	460594.53	298277.31	537373.94	384027.91	113466.9	83420.09	280587.41
pipecolinic acid	799967.06	672765.94	1258151.38	1236190.38	1139078.38	1397724.12	1512844.62	1405293.12	1101683.88	1418554.62	901813.19	1085887.38	731063.31	1180710.5	1377903.12	1218519.88
Creatine	106012136	144201872	96785320	110746616	123769112	82450088	88030256	68333064	99329720	110253344	98144536	130479320	122539072	101916288	90482952	79289912
Ornithine	3341446.25	4741349.5	4777923.5	3824204	5076536	4214786.5	4655151.5	3374824	4205984	4558202	4969500.5	3866601.75	5294449.5	4020388.25	8349463.5	3229451.75
Methylnicotinamide	4670454	4653474.5	5172454.5	3916905.25	3651681.75	3919757	4856942	2610734.25	4726591	5461704	3458699.75	4375447.5	3888247.75	1036054.06	1227400.38	2416399.25
Glutamine	98291584	107401848	130608808	117016344	114656800	110865416	110009624	115614752	125825208	112072256	125162104	115491168	127284736	124691136	135488688	118175008
Lysine	18452026	20544268	15759080	16174245	16060739	17177760	19185624	13198959	12217997	12066104	16627597	20534136	18532928	12008648	14469379	12242915
Methionine	8563359	10160408	8371868	8178636.5	10037107	7385199.5	7459894.5	4965178.5	6760910.5	6886573.5	7171918.5	8787399	9537373	4451615	6628265.5	5861588.5
Aminoadipate	635235.44	557904.44	341886.22	834053.31	586573.81	793784.19	776373.81	481151	332802.28	302704.91	309651.91	359676.75	317489.16	223475.12	234557.48	464186.09
Carnitine	52305268	70160168	60194028	73081480	84971208	54747212	54306524	59289772	43791592	35606128	26971446	44353688	59238528	53825920	57230076	38284832
3-methyl-histidine	5292108.5	4840495	5084724.5	5898708	6073996	4533777.5	5069550	4691736	6313647.5	5059519	5490427.5	5673378.5	6436666.5	3866795.25	4910011.5	4597200.5
Arginine	37676452	42205740	31345376	33878652	32471232	47751164	48367568	38399100	31385584	27224622	33819148	40646036	39239812	42884108	33651836	39217548
Guanidinosuccinic acid	13355.45	15512.74	72291.42	26838.04	27381.22	124989.22	157076.88	79087.8	31810.7	55064.11	9209.97	11504.95	16407.8	30610.94	58997.77	33785.46
Serotonin	1517730.62	1335014.88	22543.13	60734.66	2186004	2935835.75	1885422.62	1210387.88	1540770.62	452241.72	52667.75	69924.73	350418.09	1442370	1656690.88	572243.19
Glucosamine	114874.27	119202.91	122921.85	119170.62	145877.5	206951.75	230396.88	149344.25	94349.38	110068.97	80270.79	102570.3	100855.88	97076.87	86757.15	138528.48
N-Acetyl-lysine	168389.23	198581.98	194465.5	182846.2	177391.77	254401.19	336862	166788.33	139669.02	160247.98	164675.8	193976.83	156093.89	199277	225279.12	231861.89
Homoarginine	271147.62	283733.09	217674.23	217735.23	220974.17	265494.88	326193.16	249037.36	224776.61	168348.8	288710.34	299741.22	277128.66	307542.25	307593.78	220224.89
Trimethyllysine	2328641	2583701	1603392.38	2082804.62	1840091.62	2087562.38	2249503	1204762.5	2260182.75	1961643.62	1910091.62	2220417.25	2116901.75	1753538	1899850	1336865.5
Homocitrulline	142508.11	166894.2	147134.52	173658.31	178290.14	254821.14	377882.28	279575.56	195576.88	197087.11	211048.64	224038.23	187715.17	245579.23	366326.84	216447.92
Asymmetric dimethylarginine	2826467.25	2845963.75	2496689.5	2571312.75	2336250	3242323.25	3427217.25	2626524	2726652	2069893	3043317.75	3187665.25	2960823.25	3458387	3499669.25	2443514.75
O-Acetyl-L-carnitine	120797248	122173856	132054336	125398568	145886192	82264768	92214816	142757296	63685844	57791072	76142808	72948584	83078712	98008840	99912888	107782840
Kynurenine	37688.05	51711.38	36554.69	49628.21	44030.25	51925.86	73985.52	41648.58	51167.64	44597.14	35664.05	50274.07	46765.03	62116.14	75308.9	33724.72
Creatine Phosphate	729426.31	881678.5	408089.34	690623	715002.5	568276.31	443310.34	329107.16	436462.5	662185.94	804830.19	892792.75	731557.56	262244.72	263954.91	336773.72
gamma-glutamyl-alanine	93577.78	187714.33	94318.12	97104.84	109926.1	180664.05	208541.5	89679.25	86988.97	77889.4	123524.78	109678.25	161866.72	93543.2	109646.62	101142.99
Carnosine	187133.88	364087.5	91553.45	162246.81	169425.14	170232.89	150963.81	56235	212191.05	130079.69	145887.55	203951	205920.2	97255.03	101169.1	122710.63
Cystine	146348.95	70411.2	306980.38	291221.59	159466.33	375648.91	406165.91	523161.59	162474.28	148152.25	75259.54	209261.25	75611.65	91979.03	162674.94	594644.19
Anserine	268392.5	566759.5	176474.33	291799.97	278591.53	378515.34	364835	168810.31	331857.19	259532.39	227159.52	339327.28	324220.28	242855.12	266836.25	291556.72
Cytidine	191689.2	257195.64	173341.92	267418.72	198439.25	221158.3	175274.7	113269.4	227677.23	219647.5	195035.8	365528	327058.41	116901.71	221689.12	182825.52
Biotin	22240.51	23718.63	16948.75	30651.13	19449.33	21808	21802.64	6126.99	22414.17	16967.32	24732.06	33099.89	25330.79	10118.76	21826.44	15584.26
Glycerophosphocholine	4522842.5	4710216.5	4207365.5	4504584	5502453.5	2867660.75	2970874.75	2357174.75	3708396.75	2732833.75	3301790.75	4619270.5	4069051	763861.5	2644938.75	2312575
Adenosine	137399.55	79625.85	15439.94	15136.36	952890	3623669.25	872281.56	4386102.5	160702.38	12570.84	21089.24	139336.27	66883.9	517598.12	798269.69	743281.25
Glutaryl-carnitine	149746.06	302037.75	128447.25	193523.83	176143.19	103654.13	135889.38	118102.78	102324.62	88829.34	117509.34	119149.91	138485.44	147252.08	145866.83	126382.34
S-Adenosyl-homocysteine	45400.78	64298.14	14778.33	55837.22	84300.34	26409.11	21559.05	7557.05	84741.49	56470.96	17815.58	100599.34	58134.49	10172.01	105269.91	29222.75
S-Adenosylmethionine	68504.38	98438.34	46217.92	59143.56	70265.4	66342.7	75476.38	33090.95	76620.46	60357.72	49501.19	74789.3	63390.58	42337	50743.49	40208.21
Palmitoyl-Carnitine	400788	670618.69	336655.16	490090.41	370913.03	295703.81	235727.8	266978.5	365659.38	317194.78	452920.59	350436.97	467359.38	251901.75	449813.12	329934.97
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	PubChem	KEGG
Glycine	750	C00037
Pyruvate	1060	C00022
Alanine	602	C01401
Lactate	107689	C00186
Acetoacetate	96	C00164
N-Formylglycine	 75606  	-
3-Hydroxybutyric acid	441	C01089
3-hydroxyisobutyric acid	440873	C06001
Serine	5951	C00065
Glycerate	439194	C00258
Fumarate	444972	C00122
3-methyl-2-oxobutyrate	49	C00141
N-Acetylglycine	10972	-
Guanidineacetic Acid	763	C00581
Valine	6287	C00183
Succinic acid	1110	C00042
Taurine	1123	C00245
Thymine	1135	C00178
Pyroglutamate	7405	C01879
N-Acetyl-L-alanine	88064	-
trans-4-Hydroxy-L-proline	5810	C01157
Isoleucine	6306	C00407
Leucine	6106	C00123
Oxaloacetate	970	C00036
Ethylmalonic acid	11756	-
3-Ureidopropionic acid	111	C02642
Asparagine	6267	C00152
Aspartate	5960	C00049
Malate	222656	C00149
Urocanate	736715	C00785
O-Phosphoryethanolamine	1015	-
3-Methylglutaconate	1551553	-
Alpha-Ketoglutarate	51	C00026
Glutamate	33032	C00025
N-Acetyl-serine	 65249 	-
Citramalate	1081	C00815
Orotate	967	C00295
Dihydroorotic acid	648 	-
Allantoin	204	C02350
N-Methyl-L-glutamate	439377	C01046
3-Hydroxy-3-methylglutarate	1662	C03761
Fucose	17106	C01019
Phenylalanine	6140	C00079
Uric acid	1175	C00366
Dihydroxyacetone phosphate	668	C00111
Glycerol 3-phosphate	439162	C00093
N-Acetyl-Leucine	70912  	-
cis-aconitic acid	643757	C00417
N-Acetyl-aspartate	53630516 	-
Citrulline	9750	C00327
Hippuric acid	464	C01586
Glucose	5793	C00031
Tyrosine	6057	C00082
Homovanillic acid	1738	C05582
Galactitol	11850	C01697
Acetylglutamine	182230	-
N-Acetyl-glutamate	70914	-
Acetylmethionine	448580	C02712
Citrate	311	C00158
Glucuronic acid	444791	C00191
methyl beta-D-galactopyranoside	94214  	-
Gluconate	10690	C00257
Sebacic acid	5192	C08277
Tryptophan	6305	C00078
Indolelactate	676157	C02043
N-Acetyl-L-phenylalanine	74839	C03519
O-Succinyl-L-Homoserine	 439406  	-
Pantothenate	6613	C00864
Ribose 5-phosphate	440101	C00117
Thymidine	5789	C00214
Uridine	6029	C00299
N-acetyl-L-tryptophan	700653	-
Fructose 6-phosphate	69507	C00085
Glucose 6-phosphate	5958	C00092
Retinyl acetate	10245972	-
Betaine	247	C00719
Choline	305	C00114
Dimethylglycine	673	C01026
Sarcosine	1088	C00213
Hypotaurine	107812	C00519
histamine	774	C00388
Proline	145742	C00148
Nicotinamide	936	C00153
pipecolinic acid	849	C00408
Creatine	586	C00300
Ornithine	6262	C00077
Methylnicotinamide	64950 	-
Glutamine	5961	C00064
Lysine	5962	C00047
Methionine	6137	C00073
Aminoadipate	92136	C00956
Carnitine	10917	C00487
3-methyl-histidine	64969 	-
Arginine	6322	C00062
Guanidinosuccinic acid	439918	C03139
Serotonin	5202	C00780
Glucosamine	439213	C00329
N-Acetyl-lysine	265949	-
Homoarginine	9085	C01924
Trimethyllysine	440120	C03793
Homocitrulline	65072	C02427
Asymmetric dimethylarginine	123831	C03626
O-Acetyl-L-carnitine	7045767	C02571
Kynurenine	161166	C00328
Creatine Phosphate	587	C02305
gamma-glutamyl-alanine	440103	-
Carnosine	439224	C00386
Cystine	67678	-
Anserine	112072	C01262
Cytidine	6175	C00475
Biotin	171548	C00120
Glycerophosphocholine	657272	C00670
Adenosine	60961	C00212
Glutaryl-carnitine	71317118  	-
S-Adenosyl-homocysteine	439155	C00021
S-Adenosylmethionine	34756	C00019
Palmitoyl-Carnitine	 461 	-
METABOLITES_END
#END