Glutamine in the pathogenesis of hepatic encephalopathy: The Trojan horse hypothesis revisited

Kakulavarapu V. Rama Rao, Michael D Norenberg

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)593-598
Number of pages6
JournalNeurochemical Research
Volume39
Issue number3
DOIs
StatePublished - Mar 1 2014

Fingerprint

Hepatic Encephalopathy
Glutamine
Ammonia
Glutamate-Ammonia Ligase
Mitochondria
Astrocytes
Liver
Liver Diseases
Permeability
Brain
Oxidative Stress
Amino Acids
Wounds and Injuries

Keywords

  • 6-Diazo-5-oxo-l-norleucine (DON)
  • Ammonia
  • Astrocytes
  • Glutaminase
  • Glutamine
  • Hepatic encephalopathy
  • l-Histidine
  • Mitochondrial permeability transition
  • Oxidative stress

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Biochemistry

Cite this

Glutamine in the pathogenesis of hepatic encephalopathy : The Trojan horse hypothesis revisited. / Rama Rao, Kakulavarapu V.; Norenberg, Michael D.

In: Neurochemical Research, Vol. 39, No. 3, 01.03.2014, p. 593-598.

Research output: Contribution to journalArticle

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