METABOLIC EFFECTS OF COLD-STORAGE ON LIVERS FROM EUTHERMIC AND HIBERNATING COLUMBIAN GROUND-SQUIRRELS

The current study was undertaken to investigate energy metabolism duri ng hypoxia in the cold in livers from euthermic and hibernating Columb ian ground squirrels. We hypothesized that the hibernating Columbian g round squirrel would be able to maintain liver energetics for a consid erably longer time than euthermic animals. Particular reference was ma de to the function of glycolysis, which is the only mechanism for ener gy production under hypothermic ischemia. The transition from aerobic to anaerobic metabolism was apparent in both euthermic and hibernating animals as lactate levels rose within 1-3 h; total lactate accumulati on was 2.5 mu mol/g in both groups. In euthermic squirrels, liver ATP and ADP decreased considerably over the first 3-h storage; values drop ped by 55% and 34%, respectively. Conversely, as the drain on high ene rgy phosphate pools progressed, there was an increase in low energy ad enylate, AMP. Between 10 and 24 h of storage, increases in AMP account ed for approximately 25-30% of total ATP + ADP decrease. The remainder of the drop in adenylates was accounted for by considerable decreases in total adenylate (TA) contents; by 24 h TA contents had decreased b y 2.0 mu mol/g. Livers from hibernating squirrels exhibited similar pa tterns of adenylate change and were not significantly higher than thei r euthermic counterparts. With respect to regulatory control of glycol ysis, livers from euthermic squirrels exhibited no regulatory control at phosphofructokinase (PFK) or pyruvate kinase (PK). Livers from hibe rnating animals, however, showed an activation at PFK by 10 h of cold storage; levels of hexose phosphates, glucose-6-phosphate + fructose 6 -phosphate (G6P + F6P), dropped and fructose 1,6-biphosphate (F1,6P(2) ), increased. Changes in metabolite levels (phosphoenolpyruvate and py ruvate) associated with another key suspect regulatory enzyme, PK, ind icated no role in regulatory control of glycolysis during the 24-h per iod. The apparent increase in PFK responsiveness to declining energy s tores may be a futile activation since there was no accompanying incre ase in anaerobic end product lactate, and no maintenance of energetics . (C) 1996 Academic Press, Inc.