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Glutamine in the Pathogenesis of Hepatic Encephalopathy: The Trojan Horse Hypothesis Revisited.
MedLine Citation:
PMID:  23277414     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Hepatic encephalopathy (HE) is major neuropsychiatric disorder occurring in patients with severe liver disease and ammonia is generally considered to represent the major toxin responsible for this condition. Ammonia in brain is chiefly metabolized ("detoxified") to glutamine in astrocytes due to predominant localization of glutamine synthetase in these cells. While glutamine has long been considered innocuous, a deleterious role more recently has been attributed to this amino acid. This article reviews the mechanisms by which glutamine contributes to the pathogenesis of HE, how glutamine is transported into mitochondria and subsequently hydrolyzed leading to high levels of ammonia, the latter triggering oxidative and nitrative stress, the mitochondrial permeability transition and mitochondrial injury, a sequence of events we have collectively termed as the Trojan horse hypothesis of hepatic encephalopathy.
Authors:
Kakulavarapu V Rama Rao; Michael D Norenberg
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-1
Journal Detail:
Title:  Neurochemical research     Volume:  -     ISSN:  1573-6903     ISO Abbreviation:  Neurochem. Res.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7613461     Medline TA:  Neurochem Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Pathology, University of Miami Miller School of Medicine, P.O. BOX 016960, Miami, FL, 33101, USA.
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