Mechanisms of increased hepatic glutamine uptake in the endotoxin-treated rat

The mechanisms underlying the accelerated hepatic consumption of glutamine that occurs during endotoxemia were investigated in rats 12 hr after treatment with Escherichia coli lipopolysaccharide. Hepatic glutamine delivery and consumption were calculated from measurements of hepatic blood flow and blood glutamine levels. Hepatic glutaminase activity and glutamine and glutamate content were determined. Hepatocyte plasma membrane transport activity was evaluated employing isolated hepatic plasma membrane vesicles (HPMVs). Endotoxin treatment resulted in an 11-fold increase in hepatic glutamine consumption and a 2-fold increase in the delivered load of glutamine to the liver. Hepatic glutamate content doubled while glutamine content was unaffected, not withstanding a decrease in the specific activity of glutaminase. Studies employing HPMVs demonstrated that hepatic plasma membrane transport activity was unaffected by endotoxin treatment. The enhanced hepatic consumption of glutamine secondary to endotoxemia appears to be the result of both a mass-action effect and the concurrent activation of intracellular metabolism. Responses at the level of plasma membrane transport do not appear to play an active role in mediating this enhanced hepatic uptake.