Phosphoenolpyruvate Prevents the Decline in Hepatic ATP and Energy Charge after Ischemia and Reperfusion Injury in Rats

Abstract

Background: Phosphoenolpyruvate (PEP) is a high-energy metabolite in the final step of glycolysis. PEP is converted into pyruvate by pyruvate kinase. One molecule of adenosine triphosphate (ATP) is generated from one molecule of PEP. The aim of this study was to examine the effects of PEP on hepatic energy metabolism at an early phase after ischemia and reperfusion were examined in rats. Materials and methods: Male Wistar rats (250–350 g) were divided into two groups; after two 15-min periods of ischemia with 2 min reperfusion in between, either PEP or glucose solution (400 mmol/liter, pH 7.4) was infused into the portal vein (2.5 ml/300 g body wt/5 min). Before and 0, 5, 10, and 30 min after ischemia, arterial blood and liver tissue were collected for analyses. Results: During the two ischemic periods, ATP and total adenine nucleotide (TAN) of the liver decreased from 9.10 ± 0.50 and 14.06 ± 0.29 to 0.99 ± 0.50 and 10.86 ± 0.42 mmole/g liver, respectively (P< 0.05), while adenosine monophosphate (AMP) increased from 1.18 ± 0.15 to 8.47 ± 0.66 mmole/g liver (P< 0.05). Hepatic energy charge (EC) significantly decreased from 0.78 ± 0.02 to 0.16 ± 0.03 (P< 0.05). Serum concentrations of pyruvate and lactate were elevated from 1.18 ± 0.15 and 18.4 ± 0.52 to 3.29 ± 0.52 and 72.6 ± 4.8 mg/dl, respectively (P< 0.05). After a 5-min infusion of PEP or glucose solution, the ATP concentration was significantly higher in the PEP group than in the glucose group (4.08 ± 0.58 μmole/g liver vs 2.20 ± 0.45 μmole/g liver,P< 0.01), whereas AMP concentration was significantly lower in the PEP group than in the glucose group (4.26 ± 0.66 μmole/g liver vs 7.02 ± 0.71 μmole/g liver,P< 0.01). EC in the PEP group was significantly higher than that in the glucose group (0.493 ± 0.051 vs 0.293 ± 0.042,P< 0.01). Ten minutes after ischemia, the ATP, TAN, and EC levels were still higher in the PEP group than in the glucose group, but the difference did not reach statistical significance. At 30 min after ischemia, these values became similar in both groups. At 5, 10, and 30 min after ischemia, serum pyruvate concentrations were higher in the PEP group than in the glucose group. Conclusion: These findings suggest that PEP recovers hepatic energy from liver cell damage at an early phase after ischemia and reperfusion by prompt ATP production through the degradation of PEP into pyruvate in the liver.