Role of Energy Charge and Redox State for Hepatocyte Gluconeogenesis of Acutely Uremic Rats

Abstract

Hepatocytes were isolated from rats following bilateral nephrectomy, Ureter ligation or sham Operation under sodium pentobarbital (Nembutal®) anesthesia to investigate the potential role of energy Charge and redox State for the gluconeogenetic ability of liver cells. Ketogenesis from /-serine, sodium pyruvate or dihydroxyacetone was significantly higher in hepatocytes of aeutely uremic rats indicating higher concentration of reducing equivalents in the mitochondria. During ineubation, the mitochondrial redox State characterized by β-hydroxybutyrate/acetoace-tate ratio moved into direction of reduetion in all experimental groups, whereas cytosolic redox State characterized by lactate/pyruvate ratio shifted to the oxidative State indicating lack of cytosolic reducing equivalents. Hepatocyte ATP and oxoglutarate production of ureter-ligated rats were significantly higher compared with binephrectomized or sham-operated animals independent of the Substrates used. Simultaneously, energy Charge showed values higher than 0.85 only in hepatocytes of ureter-ligated animals indicating high energy supply for energy requiring processes. We conclude that hepatic gluconeogenesis and ketogenesis of aeutely uremic rats are limited by a lack of cytosolic reducing equivalents independent of cell energy supply.