Regulation of liver metabolism by enzyme phosphorylation during mammalian hibernation.
Kinetic properties of regulatory enzymes of glycolysis in liver of the mouse, Zapus hudsonius, were modified during hibernation, the probable mechanism being covalent modification. Liver glycogen phosphorylase activity was strongly depressed during both short (less than 24 h) and long (5-8 days) term hibernation, the mechanism involving a decrease in both the percentage of enzyme in the active a form and the total amount (a + b) of enzyme expressed. Phosphofructokinase showed kinetic changes (a 2.5-fold increase in Ka for fructose-2,6-P2, 4- and 3.7-fold decreases in I50 values for ATP and citrate, compared to euthermic controls) in liver of hibernators indicative of phosphorylation inactivation of the enzyme. Measured levels of fructose-2,6-P2 in liver did not change during hibernation. Changes in pyruvate kinase kinetics in liver from long term hibernators similarly indicated enzyme phosphorylation in the depressed state (Ka for fructose-1,6-P2 increased 4.4-fold, I50 for L-alanine decreased 6.3-fold). Apparent covalent modification of glycolytic enzymes during hibernation may serve two functions: depression of glycolytic activity as part of the general metabolic rate depression of hibernation, or reorganization of fuel use in the hibernating state to limit carbohydrate catabolism and promote gluconeogenesis.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002951:Citrates / Q000378:metabolism; D019343:Citric Acid; D005635:Fructosediphosphates / Q000378:metabolism; D005943:Gluconeogenesis; D006019:Glycolysis; D006605:Hibernation; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D009115:Muridae; D010732:Phosphofructokinase-1 / Q000378:metabolism; D006005:Phosphorylases / Q000378:metabolism; D010766:Phosphorylation; D011770:Pyruvate Kinase / Q000378:metabolism
D002951:Citrates; D005635:Fructosediphosphates; D019343:Citric Acid; C027652:fructose 2,6-diphosphate; D000255:Adenosine Triphosphate; D006005:Phosphorylases; D010732:Phosphofructokinase-1; D011770:Pyruvate Kinase