Hepatic metabolic changes following energy deprivation by ammonia in patients and rabbits with jaundice
Kamiyama, Y.; Takeda, H.; Ohshita, M.; Nambu, H.; Yamaoka, Y.
Surgery Gynecology and Obstetrics 145(1): 33-40
1977
ISSN/ISBN: 0039-6087 PMID: 877822 Document Number: 112555
The effects of ammonia on the energy metabolism of severely damaged liver were investigated. The enzymatic activities of carbamoylphosphate synthetase I and ornithine carbamoyltransferase in the liver did not decrease in patients with obstructive jaundice and the rabbits subjected to ligation of common bile duct. By contrast, mitochondrial phosphorylative activity was inhibited in both of them. The ability of ammonia fixation in the mitochondria of these damaged livers was inhibited because of the decreased energy supply necessary for ammonia fixation. Hyperammonemia was not observed in the patients and rabbits. In rabbits within 24 h after the ligation of common bile duct, the mortality increased with a concomitant decrease in ATP supply and adenylate energy charge in the liver. I.p. loading of ammonium chloride in the rabbits 24 h after ligation of the common bile duct caused hyperammonemia and an additional decrease in the energy charge and ATP contents in the liver. Both the energy charge and ATP contents were negatively correlated with the arteial blood ammonia levels. In the severely damaged liver in which the energy metabolism is impaired to a level at which the tissue can no longer function adequately, ammonia from the intestinal tract is fixed preferentially and deprives large amounts of hepatic energy. It is important to lower the portal vein ammonia levels in all patients with advanced liver damage, even in the absence of hyperammonemia.