Nitrogen Metabolism in Normal and Cirrhotic Liver

In the intact liver acinus, the pathways of ammonia and glutamine metabolism are embedded into a sophisticated structural and functional organization with metabolic interactions between different hepatocyte populations. This provided a new insight into the role of the liver in maintaining ammonia and bicarbonate homeostasis. A specialized cell population at the hepatic venous outflow of the liver acinus acts as a scavenger for ammonia and probably also for various signal molecules (“perivenous scavenger cell hypothesis”). Mitochondrial glutaminase and carbonic anhydrase are controlling HCO 3 - and NH 4 + input into carbamoylphosphate synthetase in periportal hepatocytes, thereby adding important targets of urea cycle flux control under physiological and pathological conditions. Chronic and acute liver diseases are associated with disturbances of this structural and functional organization. This results in a new understanding of the pathogenetic mechanism contributing to the development of hyperammonemia, acid-base disturbances and possibly other extrahepatic manifestations in liver cirrhosis.