Current state of knowledge of hepatic encephalopathy (part I): newer treatment strategies for hyperammonemia in liver failure

• Published in: Metabolic brain disease Vol. 31; no. 6; pp. 1357 - 1358
• Main Author: Kristiansen, Rune Gangsoy
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2016; Springer Nature B.V
• Subjects: Ammonia - antagonists & inhibitors; Ammonia - metabolism; Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Glutamate-Ammonia Ligase - antagonists & inhibitors; Glutamate-Ammonia Ligase - metabolism; Health Knowledge, Attitudes, Practice; Hepatic Encephalopathy - epidemiology; Hepatic Encephalopathy - metabolism; Hepatic Encephalopathy - therapy; Humans; Hyperammonemia - epidemiology; Hyperammonemia - metabolism; Hyperammonemia - therapy; Liver Failure - epidemiology; Liver Failure - metabolism; Liver Failure - therapy; Metabolic Diseases; Neurology; Neurosciences; Oncology; Ornithine - analogs & derivatives; Ornithine - pharmacology; Ornithine - therapeutic use; Short Communication; Treatment Outcome; Ornithine phenylacetate (OP); Hepatic encephalopathy; L-Ornithine L-Aspartate: treatment of hepatic encephalopathy
• ISSN: 0885-7490; 1573-7365
• DOI: 10.1007/s11011-016-9908-9

Alterations in interorgan metabolism of ammonia play an important role in the onset of hyperammonemia in liver failure. Glutamine synthetase (GS) in muscle is an important target for ammonia removal strategies in hyperammonemia. Ornithine Phenylacetate (OP) is hypothesized to remove ammonia by providing glutamate as a substrate for increased GS activity and hence glutamine production. The newly generated glutamine conjugates with phenylacetate forming phenylacetylglutamine which can be excreted in the urine, providing an excretion pathway for ammonia. We have also shown that OP targets glycine metabolism, providing an additional ammonia reducing effect.