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

• Published in: Metabolic brain disease Vol. 31; no. 6; pp. 1269 - 1273
• Main Authors: Kristiansen, Rune Gangsøy, Rose, Christopher F., Ytrebø, Lars Marius
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2016; Springer Nature B.V
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Drug Delivery Systems - trends; Glycine - antagonists & inhibitors; Glycine - metabolism; Hepatic Encephalopathy - drug therapy; Hepatic Encephalopathy - epidemiology; Hepatic Encephalopathy - metabolism; Humans; Hyperammonemia - drug therapy; Hyperammonemia - epidemiology; Hyperammonemia - metabolism; Metabolic Diseases; Neurology; Neurosciences; Oncology; Original Article; Ornithine - administration & dosage; Ornithine - analogs & derivatives; Treatment Outcome; L-ornithine-phenylacetate (OP); Phenylacetylglycine; Ammonia; Glycine; Glutamine
• ISSN: 0885-7490; 1573-7365
• DOI: 10.1007/s11011-016-9858-2

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.