Peter Pediatitakis1, Jason H. Winnike1, Justyna Wolak2, Kayvan R. Keshari1, Rex E. Jeffries1, Ryan Webb1, Greg Young3, Haakil Lee1, Michael P. Gamcsik1, Lee M. Graves4, Paul B. Watkins4, John Kurhanewizcz5, Jeffrey M. Macdonald1
1Biomedical Engineering, University of North Carolina, Chapel Hill, NC, USA; 2Liposcience Inc., Raliegh, NC, USA; 3Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA; 4Pharmacology, University of North Carolina, Chapel Hill, NC, USA; 5Radiology, University of California, San Francisco, CA, USA
We report a novel metabolomic method, mass balance phenotyping, which is based on compartmental analysis and uses empirical NMR data as input. The method employs u-13C-glucose and u-13C-glutamine to quantify metabolic flux. The pharmacodynamics (i.e., effect of drug on metabolism) is demonstrated using 2-dimensional (2D) rat hepatocytes cultured over a 48 hr period demonstrating the well-known metabolic trans-differentiation process. A rat liver cell-line (JM1) is used as a comparison. The pharmacokinetics is demonstrated using acetaminophen (APAP) exposure to 2D primary human hepatocyte cultures. The boundary conditions of the metabolic network is the interface between the cells and the media.