Control mechanisms of energy-dependent metabolic pathways in hepatocytes.

The control of respiration was studied in isolated rat-liver cells and isolated rat-liver mitochondria. When isolated rat-liver cells are perfused with different concentrations of lactate at a constant lactate/pyruvate ratio, the rate of mitochondrial respiration is a linear function of the affinity for the respiratory chain; the affinity term contains the intramitochondrial redox state and the extramitochondrial phosphate potential. However, when the cells are perfused with ammonia in addition to lactate (+ pyruvate), the stimulation of the oxygen uptake is not accompanied by an increase in the affinity. In order to obtain further insight into the relationship between oxygen uptake and intramitochondrial and extramitochondrial phosphate potential, experiments were also carried out with isolate rat-liver mitochondria incubated with an extramitochondrial ATP-utilizing system (glucose plus hexokinase) or an intramitochondrial ATP-utilizing system (citrulline synthesis). The results suggest that the rate of oxygen consumption is controlled by the intramitochondrial phosphate potential.