Stable Isotope & Metabolomics Core


Before bringing samples, fill out the order form and sample manifest, and e-mail them to Heather Zhao, so we can give you an estimate for the services needed. You will have to provide a grant number (for Einstein faculty) or get a PO number (non-Einstein faculty) to be charged for these services, you will not be charged until you receive your data. The order form, sample manifest form, and sample handling guidelines can be downloaded using the window highlighted to the right of this introduction. Please put a hard copy of sample manifest inside the samples box. You must review the markings on all tubes/samples so when a bar code is generated for your samples, there will be no confusion.

For the modules listed below, information is organized for your review of the pertinent metabolic pathways. For example in module 1 there are “hyperlinks” in the Pubchem ID and Sub pathway columns. If you click the link in Pubchem ID, it will take you to pages of information about the metabolite, including structures. If you click on the Sub pathway hyperlink, you will get taken to the small molecule pathway diagram database, and you can visualize where your metabolite is relative to others in the pathway. Clicking on a metabolite in the figure will take you to the human metabolome database for more specific information about that metabolite.


Module #1 180 Metabolites 

The targeted metabolomics approach in this assay is based on measurements with the AbsoluteIDQ p180 kit (BIOCRATES Life Sciences AG, Innsbruck, Austria). This method allows simultaneous quantification of 188 metabolites in plasma, tissues or cell pellets using liquid chromatography and flow injection analysis–mass spectrometry. For an example of this module’s utility, see: Wang-Sattler et al Novel biomarkers for pre-diabetes identified by metabolomics, Molecular Systems Biology 8; 615; doi:10.1038/msb.2012.43. 

For full list of metabolites, please click here.

Biochemical Name Pubchem ID Super Pathway Sub Pathway
Alanine 5950  Amino acids Alanine metabolism,Aspartate metabolism 
Arginine 3362  Amino acids Urea cycle, Arginine and Proline metabolism 
Asparagine 6267  Amino acids Aspartate metabolism 
Aspartic acid 5960  Amino acids Aspartate metabolism 
Citrulline 9750  Amino acids Urea cycle 
Glutamine 5961  Amino acids Glutamate metabolism 
Glutamic Acid 33032  Amino acids Glutamate metabolism 
Glycine 750  Amino acids Glycine and serine metabolism 
Histidine 6274  Amino acids Histidine metabolism 
Isoleucine 6306  Amino acids Valine, Leucine and Isoleucine Degradation 
Leucine  6106  Amino acids Valine, Leucine and Isoleucine Degradation 
Lysine 5962  Amino acids Lysine Degradation 
Methionine 6137  Amino acids Methionine metabolism 
Ornithine 6262  Amino acids Urea cycleArginine and Proline metabolism 
Phenylalanine 6140  Amino acids Phenylalanine and Tyrosine metabolism 
Proline 145742  Amino acids Arginine and Proline metabolism 
Serine 5951  Amino acids Glycine and serine metabolism 
Threonine 6288  Amino acids Threonine and 2-oxobutanoate degradation 
Tryptophan 6305  Amino acids Tryptophan metabolism 
Tyrosine 6057  Amino acids Phenylalanine and Tyrosine metabolism 
Valine 6287  Amino acids Valine,Leucine and Isoleucine metabolism 
Acetylornithine 439232  Amino acids Arginine and proline metabolism 
Asymmetric dimetylarginine 123831  Amino acids Not Available
alpha-Aminoadipic acid 469  Amino acids Lysine Degradation 
Carnosine 439224  Amino acids  beta-Alanine metabolism, Histidine metabolism 
Creatinine 588  Amino acids Creatinine 
Dopa 6047  Amino acids Catecholamine Biosynthesis 
Dopamine 681  Amino acids Catecholamine biosynthesis 
Histamine 774  Amino acids Histidine metabolism 
Kynurenine 161166  Amino acids Tryptophan Degradation,Lysine Degradation 
Methioninesulfoxide 847  Amino acids Methionine metabolism 
Nitrotyrosine 65124  Amino acids Phenylalanine and Tyrosine metabolism 
Hydroxyproline 5810  Amino acids Arginine and Proline metabolism 
Phenylethylamine 1001  Amino acids Tyrosine metabolism 
Putrescine 1045  Amino acids Spermidine and Spermine biosynthesis 
Sacrcosine 1088  Amino acids Glycine and Serine metabolism 
Symmetric dimethylarginine 169148  Amino acids Urea cycleArginine and Proline metabolism 
Serotonin 5202  Amino acids Tryptophan metabolism 
Spermidine 1102  Amino acids Spermidine and Spermine biosynthesis 
Spermine 1103  Amino acids Spermidine and Spermine biosynthesis 
Taurine 1123  Amino acids Taurine and Hypotaurine metabolism 
Total dimethylarginine 123831  Amino acids Arginine and Proline metabolism 
C0 to C18: 2 
40 species Lipid Fatty acid metabolism 
C14:0 to C44: 6 
90 species Lipid metabolism Phospholipid biosynthesis 
SM C14:1 to SM C26:1 
15 species Lipid metabolism Sphingolipid biosynthesis 
Hexose  5793  Carbohydrate Glycolysis pathwayPentose Phosphate pathway Gluconeogenesis 

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Module #2 Choline, Betaine, TMAO and Creatinine

Choline and betaine are essential nutrients. Choline is important for brain function, liver health, reproduction, and fetal and infant development. Betaine acts as a methyl donor in the liver and as an important osmolyte to protect the cells of medulla in the kidney. Their gut microbial metabolite trimethylamine N-oxide (TMAO) was considered non-toxic, but it recently has been associated with increased risk for cardiovascular disease. This finding has stimulated a growing interest in analyzing these compounds in bio fluids and studying their associations with human health and diseases. This assay allows simultaneous quantification of free choline, betaine, TMAO and creatinine in plasma, urine or tissue samples. The analysis is performed using liquid chromatography-stable isotope dilution-multiple reaction monitoring mass spectrometry (LC-SID-MRM/MS).

Biochemical Name Pubchem/Chemspider ID Pathway
Choline 305  Phospholipid Biosynthesis, Betaine Metabolism 
Betaine 247  Betaine Metabolism 
Creatinine 588  Creatinine

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Module #3 Glycolysis, Pentose Phosphate and TCA Metabolites   

Biochemical Name Pubchem ID Super Pathway Sub Pathway
Fructose-1,6-bisphosphate 445555  Carbohydrates Glycolysis pathway  
6-phospho-D-gluconate 91493  Carbohydrates Pentose Phosphate pathway  
3-phosphoglycerate 724  Carbohydrates Glycolysis, Gluconeogenesis 
Glucose-6-phosphate 5958  Carbohydrates GlycolysisGluconeogenesis 
Ribose-5-phosphate 439167  Carbohydrates Pentose Phosphate pathway 
Uridine diphosphate glucose 53477679  Carbohydrates Nucleotide sugars metabolism  
alpha-glycerol-3-phosphate 754  Carbohydrates Glycolysis pathway 
Phosphoenolpyruvate 1005  Carbohydrates GlycolysisGluconeogenesispyruvate metabolism 
alpha ketoglutaric acid 51  Carbohydrates Krebs Cycle 
Aspartic acid 5960  Carbohydrates Aspartate Metabolism, Urea Cycle  
Succinic acid 1110  Carbohydrates Krebs Cycle 
fumaric acid 444972  Carbohydrates Krebs Cycle 
Pyruvic acid 1060  Carbohydrates GlycolysisGluconeogenesispyruvate metabolism 
Lactic acid 107689  Carbohydrates GlycolysisGluconeogenesispyruvate metabolism 

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Module #4 Redox and Bioenergetics

Biochemical Name Pubchem ID Super Pathway Sub Pathway
ATP 5957  Carbohydrates Glycolysis pathway, Krebs Cycle  
ADP 6022  Carbohydrates Glycolysis pathwayKrebs Cycle  
AMP  6083  Carbohydrates Glycolysis pathwayKrebs Cycle  
NAD 5893  Carbohydrates Nicotinate and Nicotinamide metabolism 
NADH 928  Carbohydrates Nicotinate and Nicotinamide metabolism 
NADP 5886  Carbohydrates Nicotinate and Nicotinamide metabolism 
NADPH 22833512  Carbohydrates Nicotinate and Nicotinamide metabolism 





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Module #5 Bile Acids

bile acids assay

Bile acids are synthesized from cholesterol through both classical and alternative pathways. In the alternative pathway, the side chain oxidation of cholesterol precedes the steroid ring modifications, first yielding 24-, 25-, and 27-hydroxycholesterol metabolites, opposite to the process in the classical pathway. The alternative and classical pathway bile acids share the primary bile acid chenodeoxycholic acid, with 12-a-hydroxylation of chenodeoxycholic acid via CYP8B1to cholic acid. Modifications of bile acids can affect their properties and their ability to activate bile acid receptors. Dysregulation of bile acid synthesis can be seen in inborn errors of metabolism, insulin resistance, hepatocellular Ca and chronic ethanol consumption. Perturbations in the microbiome also affect bile acid pool size and composition (see references below). This panel surveys conditions of bile acid dysregulation.

Metabolite Name  Pubchem/Chemspider ID Pathway
Taurocholic acid (TCA) 6675  Bile Acid Biosynthesis 
Lithocholate (LCA) 9903  Bile Acid Biosynthesis 
Glycolithocholate (GLCA) 115245  Bile Acid Biosynthesis 
6,7-diketolithocholic acid 21403088  Bile Acid Biosynthesis 
7,12-diketolithocholic acid 22213549  Bile Acid Biosynthesis 
Glycocholate (GCA) 10140  Bile Acid Biosynthesis 
Glycoursodeoxycholic acid (GUDCA) 12310288  Bile Acid Biosynthesis 
Glycodeoxycholate (GDCA) 3035026  Bile Acid Biosynthesis 
Glycochenodeoxycholate (GCDCA) 12544  Bile Acid Biosynthesis 
Glycohyodeoxycholate (GHDCA) Steraloids
Bile Acid Biosynthesis 
Taurochenodeoxycholate (TCDCA) 387316  Bile Acid Biosynthesis 
Taurohyodeoxycholate (THDCA) 70686868  Bile Acid Biosynthesis 
Taurodeoxycholate (TDCA) 10594  Bile Acid Biosynthesis 
Deoxycholate (DCA) 222528  Bile Acid Biosynthesis 
Taurolithocholate (TLCA) 439763  Bile Acid Biosynthesis 
Omegamuricohlic acid (O-MCA)


5283851  Bile Acid Biosynthesis 
Gamma muricholic acid (G-MCA)


92805  Bile Acid Biosynthesis 
Beta-muricholic acid (ß-MCA) 5283853  Bile Acid Biosynthesis 
Alpha muricholic acid (a-MCA) 53477700  Bile Acid Biosynthesis 
Cholic acid (CA) 221493  Bile Acid Biosynthesis 
Tauro-a-muricholic acid (Ta-MCA) 101657566  Bile Acid Biosynthesis 
Tauro-ß-muricholic acid (Tß-MCA) 168408  Bile Acid Biosynthesis 


  1. More detailed pathways see Bile acid Biosynthesis, Primary Bile acid Biosynthesis, Secondary Bile acid Biosynthesis 
  2. Human insulin resistance is associated with increased plasma levels of 12a-hydroxylated bile acids Haeusler RA, Astiarraga B, Camastra S, Accili D, Ferrannini E. Diabetes. 2013 Dec; 62(12):4184-91. doi: 10.2337/db13-0639. Epub 2013 Jul 24 
  3. Application of combined omics platforms to accelerate biomedical discovery in diabesity. Kurland IJ, Accili D, Burant C, Fischer SM, Kahn BB, Newgard CB, Ramagiri S, Ronnett GV, Ryals JA, Sanders M, Shambaugh J, Shockcor J, Gross SS. Ann N Y Acad Sci. 2013 May;1287:1-16. doi: 10.1111/nyas.12116. Epub 2013 May 9. 
  4. Serum and urine metabolite profiling reveals potential biomarkers of human hepatocellular carcinoma. Chen T, Xie G, Wang X, Fan J, Qiu Y, Zheng X, Qi X, Cao Y, Su M, Wang X, Xu LX, Yen Y, Liu P, Jia W. Mol Cell Proteomics. 2011 Jul; 10(7):M110.004945. doi: 10.1074/mcp.M110.004945. Epub 2011 Apr 25. Erratum in: Mol Cell Proteomics. 2011 Nov; 10(11). doi:10.1074/mcp.A110.004945. 
  5. Alteration of bile acid metabolism in the rat induced by chronic ethanol consumption.Xie G, Zhong W, Li H, Li Q, Qiu Y, Zheng X, Chen H, Zhao X, Zhang S, Zhou Z, Zeisel SH, Jia W. FASEB J. 2013 Sep;27(9):3583-93. doi: 10.1096/fj.13-231860. Epub 2013 May 24. 
  6. Bile acids and the gut microbiome. Ridlon JM, Kang DJ, Hylemon PB, Bajaj JS.Curr Opin Gastroenterol. 2014 May;30(3):332-8 

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Module #6 Acyl CoA Analysis

This module includes acetyl CoA, malonyl CoA, and succinyl CoA, in order to interface with acyl carnitine analysis in Module #1, and TCA cycle measurements in Modules # 3 and 7.

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Module #7 GC/MS Small Metabolite Screen

GC/MS will identify about 80 to 120 small metabolites based on the difference of samples, in the combined glycolytic/gluconeogenic, pentose and TCA cycle pathways. For an example by the SIMC facility, see:

Vaitheesvaran B, Yang L, Hartil K, Glaser S, Yazulla S, et al. (2012) Peripheral Effects of FAAH Deficiency on Fuel and Energy Homeostasis: Role of Dysregulated Lysine Acetylation. PLoS ONE 7(3): e33717. doi:10.1371/journal.pone.0033717

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Module #8 Short Chain Fatty Acids

Biochemical Name  Pubchem ID HMDB Pathway
Acetic acid 176  Pyruvate Metabolism, Aspartate Metabolism, Fatty Acid Biosynthesis 
Propionic acid 1032  Propanoate Metabolism 
Butyric acid  264  Butyrate Metabolism, Fatty Acid Biosynthesis 
Isobutyric acid  6590  Not available
2-Methylbutyric acid  8314  Not available
Isovaleric acid  10430  Not available
Valeric acid  7991  Not available
2-Methylpentanoic acid  7341  Not available
3-Methylpentanoic acid  7755  Not available
4-Methylvaleric acid  12587  Not available
Hexanoic acid     8892  Fatty Acid Biosynthesis, Beta Oxidation of Very Long Chain Fatty Acids 

Module #9 Lipogenesis by Deuterated Water

Both fatty acid and cholesterol synthesis can be assessed in tissues, depending on the time frame for the study. For examples by the SIMC Facility see: 

  1. Haas et al, Hepatic Insulin Signaling Is Required for Obesity-Dependent Expression of SREBP-1c mRNA but Not for Feeding-Dependent Expression, Cell Metabolism 15, 873–884, 2012
  2. Zhao et al Regulation of lipogenesis by cyclin-dependent kinase 8–mediated control of SREBP-1, J. Clin. Invest. 122:2417-27, 2012
  3. Vaitheesvaran B, Yang L, Hartil K, Glaser S, Yazulla S, et al. (2012) Peripheral Effects of FAAH Deficiency on Fuel and Energy Homeostasis: Role of Dysregulated Lysine Acetylation. PLoS ONE 7(3): e33717 

Module #10 150~200 Metabolites in urine by LC/MS (amino acids, acylcarnitines, glycerophospholipids and sphingolipids) and untargeted GC/MS using methyl chloroformate derivatization (under development)

Biochemical Name Pubchem ID Super Pathway SubPathway
Untargeted GC/MS analysis using methyl chloroformate derivatization     see text
Acylcarnitines C0 to C18:2   Lipid metabolism Fatty acid metabolism 
Glycerophospholipids C6:0 to C44:6 92 species Lipid metabolism Phospholipid biosynthesis 
Sphingolipids SM C14:1 to SM C26:1 15 species Lipid metabolism Sphingolipid biosynthesis 

Module #11 Hepatic Recycling Glucose Tolerance Test

Module10 diagram 

Illustrative diagram of pathways for hepatic metabolism of the deuterium-labeled [2-2H1]/[6,6-2H2]glucose. Use of deutrated, instead of unlabeled glucose during a GTT allows for the estimation of hepatic and peripheral glucose disposal. Equal amounts of D1 and D2 glucose ( [2-2H1]- and [6,6-2H2] glucose) are given, at 1 mg glucose/gm body weight. De-deuteration of [2-2H1] glucose occurs during the equilibration of glucose-6-P (G-6-P) with fructose-6-P (F-6-P), which causes plasma D1/D2 levels to decrease. De-deuteration of [6,6-2H1]glucose does not occur until the deuterated glucose reaches the level of pyruvate. Whole body glucose disposal (mainly peripheral) is reflected in the area under the curve of [6,6-2H2] glucose during the GTT. Hepatic vs peripheral glucose disposal can be assessed from the differences in plasma [2-2H1]- and [6,6-2H2] glucose during the GTT. This test allows for non-invasive monitoring of peripheral and hepatic glucose disposal, and the mice can be used, after recovery, for additional phenotyping tests. GK, glucokinase; G6Pase, glucose-6-phosphatase; PK, pyruvate kinase. Diagram from Xu et al Decreased Hepatic Futile Cycling Compensates for Increased Glucose Disposal in the Pten Heterodeficient Mouse, Diabetes 55: 3372-3380, 2006.

More examples, done by the SIMC Facility:

  1. Vaitheesvaran, LeRoith and Kurland MKR mice have increased dynamic glucose disposal despite metabolic inflexibility, and hepatic and peripheral insulin insensitivity Diabetologia 53:2224–2232, 2010
  2. Vaitheesvaran et al Advantages of dynamic ‘‘closed loop’’ stable isotope flux phenotyping over static ‘‘open loop’’ clamps in detecting silent genetic and dietary phenotypes Metabolomics 6:180–190, 2010
  3. Zong et al Enhanced Energy Expenditure, Glucose Utilization, and Insulin Sensitivity in VAMP8 Null Mice Diabetes. 60: 30–38, 2011

Module #12 HGP by U13C glucose Alzet Mini-pump

The pump contains 50 mg of [U-13C6] glucose, each dissolved in 200 uL of water. The mini-pump is inserted in the subcutaneous space, and therefore infusion conditions approximate those of the venous-arterial (V-A) mode of infusion and sampling. Mass isotopomer distribution analysis is used for calculation of glucose production and recycling.


Xu, J., Xiao, G., Trujillo, C., Chang, V., Blanco, L., Chung, B. Bassilian, S., Saad, M., Tontonoz, P., Lee, W-N. P. and Kurland, I.J. (2002) PPAR alpha Influences Gluconeogenic Substrate Utilization for Hepatic Glucose Production: The Glucose Metabolome of the PPAR alpha Null Mouse. J Biol Chem. 277(52):50237-50244, PMID: 12176975


Module #13 Bioinformatics

Consultation for use and interpretation of multivariate analysis on metabolomic and lipidomic datasets

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