Brain energy metabolism in acute liver failure: studies using NMR spectroscopy

  • C. Zwingmann
  • N. Chatauret
  • D. Leibfritz
  • R. F. Butterworth


Hyperammonemia (HA) occurs in acute liver failure (ALF). When severe, ALF leads to hepatic encephalopathy (HE) (fulminant hepatic failure, FHF), which can progress to coma. Brain edema, a serious neurological complication of ALF, which may lead to increased intracranial pressure and subsequent brain herniation, remains a major cause of death in ALF.1 Evidence points to a key role for ammonia in ALF, and an ammonia-induced failure of brain energy metabolism was one of the earliest mechanisms proposed to explain the pathogenesis of HE.2 Although changes in metabolite concentrations (e.g. amino acids) have been frequently found in patients with HE and animal models of acute HE, whether or not brain energy failure occurs in ALF is still controversial, and the significance of metabolic changes in the brain in the pathogenesis of neurological complications of ALF has been repeatedly questioned. Evidence from patients with ALF, animal models of ALF, and cell culture studies suggest that ammonia directly interferes with cerebral energy metabolism in several ways, including glycolysis, the tricarboxylic acid (TCA) cycle, and the electron transport chain. In addition, impaired energy production caused by the metabolism of ammonia to glutamine may also contribute to brain energy failure, which may play a role in the pathogenesis of brain edema in ALF.


Hepatic Encephalopathy Glutamine Synthetase Brain Edema Acute Liver Failure Fulminant Hepatic Failure 
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Copyright information

© Springer Science+Business Media Dordrecht 2003

Authors and Affiliations

  • C. Zwingmann
    • 1
  • N. Chatauret
    • 1
  • D. Leibfritz
    • 2
  • R. F. Butterworth
    • 1
  1. 1.Neuroscience Research UnitCHUM Hopital Saint-LucMontrealCanada
  2. 2.Department of Organic ChemistryUniversity of BremenBremenGermany

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