Activation of hepatic glutaminase in the endotoxin-treated rat.

The basis for the accelerated hepatic utilization of glutamine that occurs during endotoxemia was investigated. In rats treated with Escherichia coli lipopolysaccharide, glutaminase activity, measured in membranes of freezed-thawed liver mitochondria, was unchanged compared with that of controls. However, flux through glutaminase in intact mitochondria was increased more than 3.5-fold by the endotoxin treatment. The effect was associated with an increase in the sensitivity of glutaminase flux to phosphate, an activator of the enzyme. These findings are similar to the activation of glutaminase by glucogenic hormones. We, therefore, propose that the increased hepatic consumption of glutamine during endotoxemia is due to an activation of glutaminase that is only evident in intact mitochondria.