The use of extracellular lactate as an oxidative substrate in the oxygen-limited frog.

The aim of this paper was to determine the contribution of anaerobic respiration to metabolism in hibernating frogs exposed to progressive hypoxia. Previous studies on acute exposure to hypoxia had shown that even at ambient PO2 levels of 60 mmHg, cold-submerged frogs were obliged to recruit anaerobic pathways to provide enough energy to maintain the ATP and phosphocreatine concentrations of tissues perfectly homeostatic. In the current experiments, we exposed frogs to hypoxic conditions gradually to reveal that 30 mmHg probably represents a 'threshold PO2' at which survival is still possible, at least for 1 week. However, by the time this threshold was reached, liver glycogen reserves were exhausted and the frog must rely thereafter on its quantitatively large store of skeletal muscle glycogen. The lactate produced as a by-product of glycolytic ATP production did not accumulate in the muscle but was preferentially exported to the plasma where it was held against a sizeable extracellular to intracellular gradient. The results suggest that the exported lactate was 'shuttled' between a poorly-perfused skeletal muscle and a more highly-perfused and oxygenated core of the animal where it could act as both a substrate for direct oxidation or for gluconeogenesis.