Metabolic adjustment and biochemical adaptation to torpor in mammalian hibernators.
Hibernating mammals have evolved the ability to lower their metabolic rate in response to temperate conditions and/or lack of food and water. At the level of enzyme control, this is accomplished by the coordinated suppression of all metabolic processes and the rearrangement of metabolic flux to maximize fuel stores. The quantification of 32 enzyme activities in 5 tissues of hibernating versus euthermic golden-mantled ground squirrels (Spermophilus lateralis) demonstrated a decreased potential in glycolysis, biosynthetic processes and carbon entry from glycolysis into the TCA cycle relative to an increased potential in fatty acid oxidation during hibernation. This was further supported by studies on ketone body metabolism, a product of fatty acid oxidation. Kinetic characterization of beta-hydroxybutyrate dehydrogenase (betaDH) and glycerol-3-phosphate dehydrogenase (G3PDH) established unique functional adaptations of these enzymes in S. lateralis and Cynomys ludovicianus. Using temperature and chemical denaturants as probes, purified G3PDH from a hibernator was found to have a greater chemical and thermal stability, and maintained both structural and functional integrity at lower temperatures relative to the enzyme from rabbits. These results purport a unique metabolic state during hibernation and demonstrate both structural and functional adaptations of hibernator enzymes to cold stress.