Metabolic Brain Disease

, Volume 31, Issue 6, pp 1269–1273 | Cite as

Glycine and hyperammonemia: potential target for the treatment of hepatic encephalopathy

  • Rune Gangsøy KristiansenEmail author
  • Christopher F. Rose
  • Lars Marius Ytrebø
Original Article


Hepatic encephalopathy (HE) is a neuropsychiatric disorder caused by hepatic dysfunction. Numerous studies dictate that ammonia plays an important role in the pathogenesis of HE, and hyperammonemia can lead to alterations in amino acid homeostasis. Glutamine and glycine are both ammoniagenic amino acids that are increased in liver failure. Modulating the levels of glutamine and glycine has shown to reduce ammonia concentration in hyperammonemia. Ornithine Phenylacetate (OP) has consistently been shown to reduce arterial ammonia levels in liver failure by modulating glutamine levels. In addition to this, OP has also been found to modulate glycine concentration providing an additional ammonia removing effect. Data support that glycine also serves an important role in N-methyl D-aspartate (NMDA) receptor mediated neurotransmission in HE. This potential important role for glycine in the pathogenesis of HE merits further investigations.


Ammonia Glutamine Glycine L-ornithine-phenylacetate (OP) Phenylacetylglycine 



Hepatic encephalopathy


Glycine cleavage system


L-ornithine Phenylacetate


Glutamine synthetase


Glutamate dehydrogenase


Acute liver failure

NMDA receptor



Non-ketotic hyperglycinemia


Compliance with ethical standards

Conflict of interest statement

None of the authors have anything to disclose.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Rune Gangsøy Kristiansen
    • 1
    • 2
    Email author
  • Christopher F. Rose
    • 3
  • Lars Marius Ytrebø
    • 1
  1. 1.Department of Anesthesiology, Anesthesia and Critical Care Research GroupUniversity Hospital of North Norway and UiT-The Arctic University of NorwayTromsøNorway
  2. 2.Department of AnesthesiologyÅlesund HospitalÅlesundNorway
  3. 3.Hepato-Neuro LaboratoryCRCHUM, Université de MontréalQCCanada

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