Metabolic regulation in mammalian hibernation: enzyme and protein adaptations.

Mammalian hibernation requires specific regulatory controls on metabolism to coordinate entry, maintenance, and arousal stages, as well as adjustments to many metabolic functions to support long-term dormancy. Several mechanisms of metabolic regulation are involved in potentiating survival. One of these is the reversible phosphorylation of regulatory enzymes, including glycogen phosphorylase, phosphofructokinase, pyruvate kinase, and pyruvate dehydrogenase. In particular, the sharp suppression of pyruvate dehydrogenase during hibernation shows the importance of control over mitochondrial oxidative metabolism for reducing metabolic rate. Fine control over specific enzymes also occurs via differential temperature effects on kinetic and allosteric properties. Analysis of temperature effects on the properties of pyruvate kinase, fructose-1,6-bisphosphatase, creatine kinase, and citrate synthase from ground squirrel or bat tissues shows a range of responses, some that would reduce enzyme activity in the hibernating state and some that would promote temperature-insensitive enzyme function. Reduced tissue phosphagen and adenylate levels, but not energy charge, may also contribute to overall metabolic suppression. New research is exploring the role of transcriptional and translational controls in hibernation via several approaches. For example, immunoblotting with antibodies to heat shock proteins (hsp 70 family) revealed the presence of constitutive hsc 70 in bat tissues but levels of the protein did not change between euthermic and hibernating states and neither the inducible hsp 70 nor the glucose-responsive protein grp 78 appeared during hibernation.