Glycolysis and energy metabolism in rat liver during warm and cold ischemia: evidence of an activation of the regulatory enzyme phosphofructokinase.

Abstract

The current study was undertaken so that the effects of both ischemia and ischemia + hypothermia could be examined in mammalian liver. Particular reference was made to the function of glycolysis, which is the only mechanism for energy production under these conditions. The response of adenylate pools reflected the energy imbalance created during warm ischemia within minutes of organ isolation. ATP levels and energy charge values for control (freshly isolated) livers were 1.20 +/- 0.07 and 0.49 +/- 0.02 mumol/g. Within 5 min of warm ischemia, ATP levels had dropped well below control values and by 30 min warm ischemia, ATP, AMP, and E.C. values were 0.21, 2.01, and 0.17 mumol/g, respectively. Cold ischemic livers (flushed with Marshall's citrate solution and stored on ice) exhibited similar, but more protracted, patterns of adenylate depletion (ATP and ADP) and accumulation (AMP). In both warm and cold ischemic livers, levels of fructose-6-phosphate (F6P) and fructose-1,6-bisphosphate (F1,6P2) indicated a marked activation of glycolysis at the phosphofructokinase (PFK) locus after a certain time of ischemia. Although the activations occurred at different times (30 min and 10 h for warm and cold ischemic livers, respectively), the patterns of change in levels of glycolytic metabolites associated with the PFK-catalyzed reaction were similar; levels of F6P dropped and F1,6P2 increased. Changes in metabolite levels (phosphoenol pyruvate and pyruvate) associated with another key suspect regulatory enzyme, pyruvate kinase, indicated no role in regulatory control of glycolysis during warm or cold ischemia. The activation of PFK at 30 min and 10 h of warm and cold ischemia, respectively, may reflect the accumulating effects of loss of intracellular homeostasis, which leads to impending irreversible damage.

• Authors: T A Churchill, K M Cheetham, B J Fuller
• Journal: Cryobiology (Cryobiology) Vol. 31 Issue 5 Pg. 441-52 (Oct 1994) ISSN: 0011-2240 [Print] Netherlands
• PMID: 7988153 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adenine Nucleotides
• Hypertonic Solutions
• Marshall's citrate solution
• Phosphofructokinase-1

Topics

• Adenine Nucleotides (metabolism)
• Animals
• Energy Metabolism
• Enzyme Activation
• Glycolysis
• Hypertonic Solutions
• In Vitro Techniques
• Ischemia (metabolism)
• Kinetics
• Liver (blood supply, injuries, metabolism)
• Male
• Organ Preservation (adverse effects, methods)
• Phosphofructokinase-1 (metabolism)
• Rats
• Temperature