Interorgan ammonia metabolism in liver failure: the basis of current and future therapies.
Hepatic encephalopathy complicates the course of both acute and chronic liver disease and its treatment remains an unmet clinical need. Ammonia is thought to be central in its pathogenesis and remains an important target of current and future therapeutic approaches. In liver failure, the main detoxification pathway of ammonia metabolism is compromised leading to hyperammonaemia. In this situation, the other ammonia-regulating pathways in multiple organs assume important significance. The present review focuses upon interorgan ammonia metabolism in health and disease describing the role of the key enzymes, glutamine synthase and glutaminase. Better understanding of these alternative pathways are leading to the development of new therapeutic approaches.
Wright
Gavin
G
UCL Institute of Hepatology, Division of Medicine, University College London, London, UK.
Noiret
Lorette
L
Olde Damink
Steven W M
SW
Jalan
Rajiv
R
D000273:Adipose Tissue / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism*; D001120:Arginine / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism; D004151:Dipeptides / Q000627:therapeutic use; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D005972:Glutaminase / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D006801:Humans; D022124:Hyperammonemia / Q000209:etiology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D017093:Liver Failure / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D010654:Phenylbutyrates / Q000627:therapeutic use; D020160:Sodium Benzoate / Q000627:therapeutic use
D000596:Amino Acids; D004151:Dipeptides; D010654:Phenylbutyrates; D000641:Ammonia; D001120:Arginine; D005972:Glutaminase; D005974:Glutamate-Ammonia Ligase; C002939:ornithylaspartate; D020160:Sodium Benzoate