subtilis enzyme is inhibited by AMP, though this can be overcome by phosphoenolpyruvate, and is dependent on Mn(2+). Mutants lacking this enzyme are apparently still able to grow on gluconeogenic growth substrates such as malate and glycerol. Interactive pathway map Hibernation and cold adaptation Fructose 1,6-bisphosphatase also plays a key role in hibernation, which requires strict regulation of metabolic processes to facilitate entry into hibernation, maintenance, arousal from hibernation, and adjustments to allow long-term dormancy. During hibernation, an animal's metabolic rate may decrease to around 1/25 of its euthermic resting metabolic rate. FBPase is modified in hibernating animals to be much more temperature sensitive than it is in euthermic animals. FBPase in the liver of a hibernating bat showed a 75% decrease in Km for its substrate FBP at 5 °C than at 37 °C. However, in a euthermic bat this decrease was only 25%, demonstrating the difference in temperature sensitivity between hibernating and euthermic bats. When sensitivity to allosteric inhibitors such as AMP, ADP, inorganic phosphate, and fructose-2,6-bisphosphate were examined, FBPase from hibernating bats was much more sensitive to inhibitors at low temperature than in euthermic bats. During hibernation, respiration also dramatically decreases, resulting in conditions of relative anoxia in the tissues. Anoxic conditions inhibit gluconeogenesis, and therefore FBPase, while stimulating glycolysis, and this is another reason for reduced FBPase activity in hibernating animals. The substrate of FBPase, fructose 1,6-bisphosphate, has also been shown to activate pyruvate kinase in glycolysis, linking increased glycolysis to decreased gluconeogenesis when FBPase activity is decreased during hibernation. In addition to hibernation, there is evidence that FBPase activity varies significantly between warm and cold seasons even for animals that do not hibernate. In rabbits exposed to cold temperatures, FBPase activity decreased throughout the duration of cold exposure, increasing when temperatures became warmer again. The mechanism of this FBPase inhibition is thought to be digestion of FBPase by lysosomal proteases, which are released at higher levels during colder periods. Inhibition of FBPase through proteolytic digestion decreases gluconeogenesis relative to glycolysis during cold periods, similar to hibernation. Fructose 1,6-bisphosphate aldolase is another temperature dependent enzyme that plays an important role in the regulation of glycolysis and gluconeogenesis during hibernation. Its main role is in glycolysis instead of gluconeogenesis, but its substrate is the same as FBPase's, so its activity affects that of FBPase in gluconeogenesis. Aldolase shows similar changes in activity to FBPase at colder temperatures,