The liver shows net glutamine uptake after a protein-containing meal, durin
g uncontrolled diabetes, sepsis and short-term starvation, but changes to n
et release during long-term starvation and metabolic acidosis. Some studies
report a small net release of glutamate by the liver. The differential exp
ression of glutamine synthetase (perivenous) and glutaminase (periportal) w
ithin the liver indicates that glutamine is used for urea synthesis in peri
portal cells, whereas glutamine synthesis serves to detoxify any residual a
mmonia in perivenous cells. Experiments in vivo suggest that changes in net
hepatic glutamine balance are due predominantly to regulation of glutamina
se activity, with the flux through glutamine synthetase being relatively co
nstant.