LIVER-METABOLISM IN COLD HYPOXIA - A COMPARISON OF ENERGY-METABOLISM AND GLYCOLYSIS IN COLD-SENSITIVE AND COLD-RESISTANT MAMMALS

The effects of cold hypoxia were examined during a time-course at 2 de grees C on levels of glycolytic metabolites: glycogen, glucose, glucos e-1-phosphate, glucose-6-phosphate, fructose-6-phosphate, fructose-1,6 -bisphosphate, phosphoenolpyruvate, pyruvate, lactate and energetics ( ATP, ADP, AMP) of livers from rats and columbian ground squirrels. Res ponses of adenylate pools reflected the energy imbalance created durin g cold hypoxia in both rat and ground squirrel liver within minutes of organ isolation. In rat, ATP levels and energy charge values for fres hly isolated livers were 2.54 mu mol.g(-1) and 0.70, respectively. Wit hin 5 min of cold hypoxia, ATP levels had dropped well below control v alues and by 8 h storage, ATP, AMP, and energy charge values were 0.21 mu mol.g(-1), 2.01 mu mol g(-1), and 0.17, respectively. In columbian ground squirrels the patterns of rapid ATP depletion and AMP accumula tion were similar to those found in rat. In rat liver, enzymatic regul atory control of glycolysis appeared to be extremely sensitive to the decline in cellular energy levels. After 8 h cold hypoxia levels of fr uctose-6-phosphate decreased and fructose-1,6-bisphosphate increased, thus reflecting an activation of glycolysis at the regulatory step cat alysed by phosphofructokinase fructose-1,6-bisphosphatase. Despite an initial increase in flux through glycolysis over the first 2 min (lact ate levels increased 3.7 mu mol g(-1)), further flux through the pathw ay was not permitted even though glycolysis was activated at the phosp hofructokinase/fructose-1,6-bisphosphatase locus at 8 h, since supplie s of phosphorylated substrate glucose-1-phosphate or glucose-6-phospha te remained low throughout the duration of the 24-h period. Conversely , livers of Columbian ground squirrels exhibited no activation or inac tivation of two key glycolytic regulatory loci, phosphofructokinase/fr uctose-1,6-bisphosphatase and pyruvate kinase/phosphoenolpyruvate carb oxykinase and pyruvate carboxylase. Although previous studies have sho wn similar allosteric sensitivities to adenylates to rat liver phospho fructokinase, there was no evidence of an activation of the pathway as a result of decreasing high energy adenylate, ATP or increasing AMP l evels. The lack of any apparent regulatory control of glycosis during cold hypoxia may be related to hibernator-specific metabolic adaptatio ns that are key to the survival of hypothermia during natural bouts of hibernation.