Liver glutamine metabolism

A fundamental conceptional change in the field of hepatic glutamine metabolism is derived from an understanding of the unique regulatory properties of hepatic glutaminase, the occurrence of glutamine cycling, and the discovery of marked hepatocyte heterogeneities in nitrogen metabolism, with metabolic interactions between differently localized subacinar hepatocyte populations. This change provided new insight into the role of the liver in maintaining ammonia and bicarbonate homeostasis under physiologic and pathologic conditions. Glutamine synthetase is present only in a specialized cell population at the hepatic venous outflow of the liver acinus; these cells act as scavengers for ammonia and probably also for various signal molecules ("perivenous scavenger cell hypothesis"). The function of mitochondrial glutaminase is that of a pH- and hormone-modulated ammonia amplification system that controls carbamoylphosphate synthesis and urea cycle flux in periportal hepatocytes. Not only is hepatic glutamine metabolism essential for maintenance of bicarbonate and ammonia homeostasis, but glutamine itself can act in the liver as a signal modulating hepatic metabolism. This article summarizes some major aspects of hepatic glutamine metabolism, based on previous reviews.