Cutaneous burn injury alters relative tricarboxylic acid cycle fluxes in rat liver

Severe injury induces a hypermetabolic state in the liver; however, the pat hways that are responsible for the increase in hepatic energy demand have n ot been identified. Relative fluxes in the tricarboxylic acid (TCA) cycle m ere determined in perfused livers from rats 4 days after administration of a cutaneous burn injury. The perfusate was supplemented with 5 mM uniformly labeled C-13-laaate to efficiently label intracellular metabolites. Flux r atios mere calculated on the basis of (1) the C-13-labeling pattern of the glutamate and lactate isotopomers within the liver as determined by nuclear magnetic resonance spectroscopy and (2) an isotopomer mass balance model o f the TCA cycle. Calculated flux ratios suggest that burn injury results in an increase in the contribution of pyruvate to the oxaloacetate pool at th e expense of non-TCA cycle sources. Furthermore, a dramatic increase in C-1 3-labeling of glucose was observed in burned rat livers. These data taken t ogether suggest that burn injury induces intrinsic changes in intrahepatic metabolism, including an alteration of the relative fluxes consistent with increased gluconeogenesis from lactate.