The basis for the accelerated hepatic utilization of glutamine that oc
curs during endotoxemia was investigated. In rats treated with Escheri
chia coli lipopolysaccharide, glutaminase activity, measured in membra
nes of freezed-thawed liver mitochondria, was unchanged compared with
that of controls. However, flux through glutaminase in intact mitochon
dria was increased more than 3.5-fold by the endotoxin treatment. The
effect was associated with an increase in the sensitivity of glutamina
se flux to phosphate, an activator of the enzyme. These findings are s
imilar to the activation of glutaminase by glucogenic hormones. We, th
erefore, propose that the increased hepatic consumption of glutamine d
uring endotoxemia is due to an activation of glutaminase that is only
evident in intact mitochondria. (C) 1995 Academic Press, Inc.