Influence of precursors of biosyntheses on the energy metabolism of the liver cell.

The influence of variable energy demand on both the total ATP/ADP ratio and the rate of respiration was investigated in isolated hepatocytes. For hepatocytes respiring at the same rate, different ATP/ADP ratios were observed when the energy drain was caused either by ureogenesis and gluconeogenesis or by partial uncoupling. These differences were provoked by an additional effect of the precursors of syntheses studied, i.e. lactate or ornithine, on the hydrogen supply of the respiratory chain, as was reflected in terms of the reduction degree of cytochrome c in isolated mitochondria. For a fixed hydrogen supply there exists a defined characteristic ATP/ADP ratio versus rate of respiration. It is concluded that the respiratory rate, the mitochondrial redox state and the phosphorylation potential (transmitted into the extramitochondrial one by the adenine nucleotide translocator) represent a system of three interdependent parameters. The presence of metabolic precursors such as ornithine and lactate enhances the load of the cellular energy metabolism as well as the energy supply of the cell, the latter through improvement of substrate utilization. The ambivalent character of the precursors makes possible a kind of forward optimization of the hepatic energy metabolism which allows the cell to perform syntheses at a relatively high ATP/ADP ratio and, unless syntheses take place, to save energy by avoiding higher ATP/ADP ratios.