Profound alterations in the regulation of energy and amino acid metabolism occur after burn injury. Given that the liver plays a major role in regulating whole body amino acid metabolism and is the primary site of nitrogen conversion into urea, we hypothesize that burn injury induces intrinsic metabolic changes in liver, and that these changes are responsible in large part for the aberrant amino acid profile as well as the increased nitrogen loss in the patient after burns. The overall objective of the proposed studies is to investigate, in a well characterized and controlled perfused liver model, the molecular mechanisms which trigger the overall metabolic changes that occur in the liver in response to burn trauma, and how these changes affect the metabolism of conditionally essential amino acids and the conversion of amino acid nitrogen into urea.
The specific aims of the proposed work are: 1. To determine the mechanisms of increased amino acid oxidation in burned rat liver. 2. To determine the mechanisms of increased urea production in the burned rat liver and identify critical urea and TCA cycle interactions. The proposed studies will provide basic, quantitative information on the pathways activated by burn injury in liver and on the molecular mechanisms which mediate this activation. This investigation will form a rational basis for (1) the future development of nutritional regimens and therapeutic approaches aimed at reducing the catabolic response to burn injury, and (2) for the investigation of the gene expression component in the modulation of amino acid oxidation.
| Orman, Mehmet A; Arai, Kosuke; Yarmush, Martin L et al. (2010) Metabolic flux determination in perfused livers by mass balance analysis: effect of fasting. Biotechnol Bioeng 107:825-35 |
| Yokoyama, Tadaaki; Banta, Scott; Berthiaume, Francois et al. (2005) Evolution of intrahepatic carbon, nitrogen, and energy metabolism in a D-galactosamine-induced rat liver failure model. Metab Eng 7:88-103 |
| Berthiaume, Francois; MacDonald, Annette D; Kang, Yoon H et al. (2003) Control analysis of mitochondrial metabolism in intact hepatocytes: effect of interleukin-1beta and interleukin-6. Metab Eng 5:108-23 |
| Kang, Yoon H; Berthiaume, Francois; Yarmush, Martin L (2002) Long-term stable cultures of rat hepatocytes: an in vitro model to study acute and chronic hepatic inflammation. Tissue Eng 8:681-93 |
| Arai, K; Lee, K; Berthiaume, F et al. (2001) Intrahepatic amino acid and glucose metabolism in a D-galactosamine-induced rat liver failure model. Hepatology 34:360-71 |
