Corin O'Dell Miller1, Haiying Liu1, Leslie Balogh2, Jin Cao1, Mike R. Tota3, Reshma Patel3
1Imaging, Merck, Rahway, NJ, USA; 2Laboratory Animal Research, Merck, Rahway, NJ, USA; 3Metabolic Disorders, Merck, Rahway, NJ, USA
A 13C MRS approach was employed in perfused mouse livers metabolizing substrate levels of [2-13C] pyruvate to develop a novel ex-vivo marker of pyruvate recycling based on the 13C-enrichment in lactate. Inhibition of each of the pyruvate recycling pathways (PEPCK via 3-mercapto-picolinic acid, and Malic enzyme via tartronic acid) reduced this marker in liver extracts while simultaneous inhibition of each pathway further reduced this marker to levels near the LOQ. Real time data from whole perfused livers agreed with data from extracts of freeze-clamped livers indicating that this approach may be translatable to whole tissues and possibly in vivo.