METABOLIC-REGULATION IN MAMMALIAN HIBERNATION - ENZYME AND PROTEIN ADAPTATIONS

Mammalian hibernation requires specific regulatory controls on metabol ism to coordinate entry, maintenance, and arousal stages, as well as a djustments to many metabolic functions to support long-term dormancy. Several mechanisms of metabolic regulation are involved in potentiatin g survival. One of these is the reversible phosphorylation of regulato ry enzymes, including glycogen phosphorylase, phosphofructokinase, pyr uvate kinase, and pyruvate dehydrogenase. In particular, the sharp sup pression of pyruvate dehydrogenase during hibernation shows the import ance of control over mitochondrial oxidative metabolism for reducing m etabolic rate. Fine control over specific enzymes also occurs via diff erential temperature effects on kinetic and allosteric properties. Ana lysis of temperature effects on the properties of pyruvate kinase, fru ctose-1,6-bisphosphatase, creatine kinase, and citrate synthase from g round squirrel or bat tissues shows a range of responses, some that wo uld reduce enzyme activity in the hibernating state and some that woul d promote temperature-insensitive enzyme function. Reduced tissue phos phagen and adenylate levels, hut not energy charge, may also contribut e to overall metabolic suppression. New research is exploring the role of transcriptional and translational controls in hibernation via seve ral approaches. For example, immunoblotting with antibodies to heat sh ock proteins (hsp 70 family) revealed the presence of constitutive hsc 70 in bat tissues but levels of the protein did not change between eu thermic and hibernating states and neither the inducible hsp70 nor the glucose-responsive protein grp78 appeared during hibernation. (C) 199 7 Elsevier Science Inc.