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

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Abstract

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.

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Abbreviations

HE:

Hepatic encephalopathy

GCS:

Glycine cleavage system

OP:

L-ornithine Phenylacetate

GS:

Glutamine synthetase

GDH:

Glutamate dehydrogenase

ALF:

Acute liver failure

NMDA receptor:

N-methyl–D-aspartate

NKH:

Non-ketotic hyperglycinemia

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Authors and Affiliations

  1. Department of Anesthesiology, Anesthesia and Critical Care Research Group, University Hospital of North Norway and UiT-The Arctic University of Norway, Tromsø, Norway

    Rune Gangsøy Kristiansen & Lars Marius Ytrebø

  2. Department of Anesthesiology, Ålesund Hospital, Helse Møre og Romsdal, 6010, Ålesund, Norway

    Rune Gangsøy Kristiansen

  3. Hepato-Neuro Laboratory, CRCHUM, Université de Montréal, Montréal, QC, Canada

    Christopher F. Rose

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  1. Rune Gangsøy Kristiansen
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  2. Christopher F. Rose
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  3. Lars Marius Ytrebø
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Correspondence to Rune Gangsøy Kristiansen.

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Kristiansen, R.G., Rose, C.F. & Ytrebø, L.M. Glycine and hyperammonemia: potential target for the treatment of hepatic encephalopathy. Metab Brain Dis 31, 1269–1273 (2016). https://doi.org/10.1007/s11011-016-9858-2

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