title: Current state of knowledge of hepatic encephalopathy (part I): newer treatment strategies for hyperammonemia in liver failure.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Anesthesia and Critical Care Research Group, University Hospital of North Norway, UiT-The Arctic University of Norway, Tromsø, Norway. rune_ga_kri@outlook.com.
authors.forename: Rune Gangsoy
authors.initials: RG
authors.lastname: Kristiansen
mesh_terms: D000641:Ammonia / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D005974:Glutamate-Ammonia Ligase / Q000037:antagonists & inhibitors / Q000378:metabolism; D007722:Health Knowledge, Attitudes, Practice; D006501:Hepatic Encephalopathy / Q000453:epidemiology / Q000378:metabolism* / Q000628:therapy*; D006801:Humans; D022124:Hyperammonemia / Q000453:epidemiology / Q000378:metabolism* / Q000628:therapy*; D017093:Liver Failure / Q000453:epidemiology / Q000378:metabolism / Q000628:therapy; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000641:Ammonia; C572232:ornithine phenylacetate; D009952:Ornithine; D005974:Glutamate-Ammonia Ligase
keywords: Hepatic encephalopathy; L-Ornithine L-Aspartate: treatment of hepatic encephalopathy; Ornithine phenylacetate (OP)