Hepatic glutamine metabolism

Expression of high activities of both glutamine synthetase and glutaminase allows the liver to play a major role in the regulation of glutamine homeostasis. The liver shows net glutamine output in metabolic acidosis, in prolonged starvation and animals bearing tumors, net glutamine uptake in the postabsorptive state, on consuming high protein diets, and in uncontrolled diabetes or sepsis. Liver glutamine synthetase is expressed only in a small population of perivenous cells that allows it to salvage any ammonia not incorporated into urea in periportal cells. Hepatic glutaminase is a unique isozyme found only in periportal liver parenchymal cells where it provides glutamate and ammonia for the urea cycle. Control of hepatic glutamine metabolism occurs almost exclusively through changes in the activity of glutaminase, with no change in glutamine synthetase flux.