Limited capacity for ammonia removal by brain in chronic liver failure: potential role of nitric oxide.

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Rose C, Felipo V

Limited capacity for ammonia removal by brain in chronic liver failure: potential role of nitric oxide.

Metab Brain Dis. 2005 Dec;20(4):275-83.

PubMed ID

16382338 [ View in PubMed

]

Abstract

Chronic liver failure leads to hyperammonemia and consequently increased brain ammonia concentrations, resulting in hepatic encephalopathy. When the liver fails to regulate ammonia concentrations, the brain, devoid of a urea cycle, relies solely on the amidation of glutamate to glutamine through glutamine synthetase, to efficiently clear ammonia. Surprisingly, under hyperammonemic conditions, the brain is not capable of increasing its capacity to remove ammonia, which even decreases in some regions of the brain. This non-induction of glutamine synthetase in astrocytes could result from possible limiting substrates or cofactors for the enzyme, or an indirect effect of ammonia on glutamine synthetase expression. In addition, there is evidence that nitration of the enzyme resulting from exposure to nitric oxide could also be implicated. The present review summarizes these possible factors involved in limiting the increase in capacity of glutamine synthetase in brain, in chronic liver failure.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
L-Glutamine	Glutamine synthetase	Protein	Humans	Unknown	Product of	Details