Phosphofructokinase of the Hibernator Citellus beecheyi: Temperature and pH Regulation of Activity via Influences on the Tetramer-Dimer Equilibrium

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Abstract
During transitions between hibernating and euthermic states, the rates and types of metabolism occurring in small mammalian hibernators undergo major adjustments. Total metabolic rate is severely reduced, and shifts between different fuels for energy metabolism occur. To elucidate the enzyme regulatory mechanisms responsible for these types of metabolic changes, we have examined the influences of temperature and pH on skeletal muscle phosphofructokinase (PFK) purified from the California ground squirrel, Citellus beecheyi. The acidification that occurs during entry into hibernation, approximately 0.3-0.4 pH units, acts synergistically with falling body temperature to promote a large inhibition of PFK activity. This temperature-pH effect is enhanced by the presence of low (25 mM) concentrations of urea. The loss of PFK activity is shown to be due to the freely reversible conversion of the active, tetrameric form of the enzyme to the catalytically inactive, but structurally native, dimeric state of PFK. Restoration of euthermic conditions of temperature and pH lead to rapid restoration of the tetrameric state and, thus, to PFK activity. Regulatory effects of these types could be important in reversibly inhibiting glycolytic flux during entry into hibernation and thereby eliminating the potential for shivering thermogenesis, while conserving muscle glycogen stores for thermogenesis during arousal and for bouts of locomotory activity following arousal.