Review
Metabolic regulation in mammalian hibernation: Enzyme and protein adaptations

https://doi.org/10.1016/S0300-9629(97)00238-7Get rights and content

Abstract

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.

References (46)

  • L.J. Reed et al.

    Pyruvate dehydrogenase

  • K.B. Storey

    Regulation of liver metabolism by enzyme phosphorylation during mammalian hibernation

    J. Biol. Chem.

    (1987)
  • K.B. Storey

    Metabolic adaptations supporting anoxia tolerance in reptiles: Recent advances

    Comp. Biochem. Physiol. B

    (1996)
  • Z. Yu et al.

    Monoclonal antibody ELISA test indicates that large amounts of constitutive hsp-70 are present in salamanders, turtle and fish

    J. Therm. Biol.

    (1994)
  • B.O. Andersen et al.

    Fatty acid synthetase in control, starved, and refed Richardson's ground squirrels

    Comp. Biochem. Physiol.

    (1989)
  • J.R. Aprille

    Regulation of the mitochondrial adenine nucleotide pool size in liver: Mechanism and metabolic role

    FASEB J.

    (1988)
  • A.I. Borgmann et al.

    Enzymes of the normothermic and hibernating bat, Myotis lucifugus: Temperature as a modulator of pyruvate kinase

    J. Comp. Physiol.

    (1976)
  • S.P.J. Brooks et al.

    Mechanisms of glycolytic control during hibernation in the ground squirrel Spermophilus lateralis

    J. Comp. Physiol.

    (1992)
  • Brooks, S.P.J.; Storey, K.B. Mechanisms of metabolic arrest in land...
  • D.L. Denlinger et al.

    Role of chilling in the acquisition of cold tolerance and the capacitation to express stress proteins in diapausing pharate larvae of the gypsy moth, Lymantria dispar

    Arch. Insect Biochem. Physiol.

    (1992)
  • K.N. Ekdahl et al.

    The effect of fructose-2,6-bisphosphate and AMP on the activity of phosphorylated and unphosphorylated fructose-1,6-bisphosphatase from rat liver

    FEBS Lett.

    (1984)
  • F. Geiser

    Reduction of metabolism during hibernation and daily torpor in mammals and birds: Temperature effect or physiological inhibition

    J. Comp. Physiol.

    (1988)
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    Supported by a research grant from the N.S.E.R.C. Canada.

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